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1. Association Between Planned Cesarean Delivery and Neonatal Mortality and Morbidity in Twin Pregnancies

Author: Olivier Graesslin, Corinne Dupont, Philippe Deruelle, Michel Dreyfus, Olivier Parant, Fabrice Pierre, Bruno Langer, Pierre Chabanier, Gilles Kayem, Franck Perrotin, René-Charles Rudigoz, Françoise Venditelli, Patrice Poulain, Christophe Vayssière, Norbert Winer, Didier Riethmuller, Loïc Marpeau, C. Prunet, Caroline Bohec, François Goffinet, Eric Verspyck, Loïc Sentilhes, Thomas Schmitz, Patrick Rozenberg, Claude D'Ercole, Pierre-Yves Ancel, Renaud de Tayrac, Olivier Morel, Jean Gondry, Marie-Victoire Senat, Paul Sagot, André Bongain, Laurence Lecomte-Raclet, Elie Azria, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Service de Gynécologie-Obstétrique (Gynéco-Obs - PAU), Hôpital François Mitterand (PAU - Hop F Mitterand), Service de Gynécologie-Obstétrique-Reproduction, Hôpital l'Archet, Service de Gynécologie - Obstétrique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de gynécologie-obstétrique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Toulouse [Toulouse], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Gynécologie-Obstétrique [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Réseau périnatal Aurore, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Departments of Gynaecology and Obstetrics, Clinical Science Institute-National University of Ireland [Galway] (NUI Galway), Service de gynécologie-obstétrique [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département d'échographie et de Médecine fœtale, SIHCUS-CMCO, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Service de gynécologie et obstétrique [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Centre hospitalier universitaire régional de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de gynécologie et obstétrique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gynécologie-Obstétrique ( Gynéco-Obs - PAU ), Hôpital François Mitterand ( PAU - Hop F Mitterand ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Service de Gynécologie - Obstétrique et médecine de la reproduction [Caen], CHU Caen, Santé Individu Société - SIS ( SIS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Hospices Civils de Lyon ( HCL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon III-Université Lumière - Lyon 2 ( UL2 ), Transporteurs membranaires, chimioresistance et drug-design ( TMCD2 ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-Institut Mère Enfant, Service de gynécologie-obstétrique [Caen], Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), CHRU Tours, Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale, ToxAlim ( ToxAlim ), Institut National Polytechnique [Toulouse] ( INP ) -Institut National de la Recherche Agronomique ( INRA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Ecole Nationale Vétérinaire de Toulouse, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Clinical Science Institute-National University of Ireland [Galway] ( NUI Galway ), CHU Angers, Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Physiologie des Adaptations Nutritionnelles ( PhAN ), Institut National de la Recherche Agronomique ( INRA ) -Université de Nantes ( UN ), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)
Subjects: Male, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Population, Twins, Gestational Age, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Infant, Newborn, Diseases, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Infant Mortality, Medicine, Childbirth, Humans, Caesarean section, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, education, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, ComputingMilieux_MISCELLANEOUS, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Cesarean Section, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.disease, Infant mortality, 3. Good health, Obstetric Labor Complications, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Cohort study
Abstract: International audience; OBJECTIVE: To evaluate the association between the planned mode of delivery and neonatal mortality and morbidity in an unselected population of women with twin pregnancies. METHODS: The JUmeaux MODe d'Accouchement (JUMODA) study was a national prospective population-based cohort study. All women with twin pregnancies and their neonates born at or after 32 weeks of gestation with a cephalic first twin were recruited in 176 maternity units in France from February 2014 to March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Comparisons were performed according to the planned mode of delivery, planned cesarean or planned vaginal delivery. The primary analysis to control for potential indication bias used propensity score matching. Subgroup analyses were conducted, one according to gestational age at delivery and one after exclusion of high-risk pregnancies. RESULTS: Among 5,915 women enrolled in the study, 1,454 (24.6%) had planned cesarean and 4,461 (75.4%) planned vaginal deliveries, of whom 3,583 (80.3%) delivered both twins vaginally. In the overall population, composite neonatal mortality and morbidity was increased in the planned cesarean compared with the planned vaginal delivery group (5.2% compared with 2.2%; odds ratio [OR] 2.38, 95% confidence interval [CI] 1.86–3.05). After matching, neonates born after planned cesarean compared with planned vaginal delivery had higher composite neonatal mortality and morbidity rates (5.3% compared with 3.0%; OR 1.85, 95% confidence interval 1.29–2.67). Differences in composite mortality and morbidity rates applied to neonates born before but not after 37 weeks of gestation. Multivariate and subgroup analyses after exclusion of high-risk pregnancies found similar trends.CONCLUSION: Planned vaginal delivery for twin pregnancies with a cephalic first twin at or after 32 weeks of gestation was associated with low composite neonatal mortality and morbidity. Moreover, planned cesarean compared with planned vaginal delivery before 37 weeks of gestation might be associated with increased composite neonatal mortality and morbidity.
Published: 2017
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2. MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

Author: Julie Kennedy, Chunmei Li, Marta Romani, Enza Maria Valente, Victor L. Jensen, Jean Baptiste Rivière, Michel R. Leroux, Jeremy F. Reiter, Estelle Lopez, Kwangjin Park, Francesc R. Garcia-Gonzalo, Laurence Faivre, Bérénice Doray, Oliver E. Blacque, Christel Thauvin-Robinet, Roberta De Mori, Ange Line Bruel, Dominique Gaillard, Department of Molecular Biology and Biochemistry ( MBB ), Simon Fraser University ( SFU.ca ), School of Biology & Environmental Science and Conway Institute of Biomolecular & Biomedical Research, University College Dublin, University College Dublin [Dublin] ( UCD ), Cardiovascular Research Institute ( CVRI ), Univerisity of California ( UCSF ), IRCCS 'Casa Sollievo della Sofferenza', Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Service de Génétique, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), Service de Génétique Médicale, Hôpital Civil, Strasbourg, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), voestalpine Stahl Donawitz GmbH, Department of Biochemistry & Biophysics, University of California [San Francisco] ( UCSF ), Canadian Institutes of Health Research (CIHR) MOP 142243 March of Dimes Michael Smith Foundation for Health Research (MSFHR) European Research Council (ERC) 260888 Telethon Foundation Italy GGP13146 Science Foundation Ireland SFI-111037 European Community's Seventh Framework Programme (SYSCILIA) 241955 NIH AR054396 GM095941 Burroughs Wellcome Fund Packard Foundation Sandler Family Supporting Foundation GIS-Institut des Maladies Rares French Fondation for Rare Disease French Ministry of Health (PHRC) 2010-A01014-35 Regional Council of Burgundy Vanier Canada Graduate Scholarship MSFHR postdoctoral fellowship KRESCENT postdoctoral fellowship, Department of Molecular Biology and Biochemistry (MBB), Simon Fraser University (SFU.ca), University College Dublin [Dublin] (UCD), Cardiovascular Research Institute (CVRI), University of California [San Francisco] (UCSF), University of California-University of California, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: 0301 basic medicine, Nematoda, Cell Membranes, Peripheral Membrane Proteins, Gene Identification and Analysis, syndrome type vi, Animal Cells, Medicine and Health Sciences, Biology (General), Caenorhabditis elegans, Connective Tissue Cells, Genetics, biology, General Neuroscience, Cilium, Ciliary transition zone, joubert syndrome, Animal Models, Orofaciodigital Syndromes, Cyclin-Dependent Kinases, 3. Good health, Cell biology, Phenotypes, Connective Tissue, RPGRIP1L, c-elegans, flagella, Cellular Structures and Organelles, Cellular Types, Anatomy, General Agricultural and Biological Sciences, Microtubule-Associated Proteins, primary cilium, Research Article, Microtubule-associated protein, QH301-705.5, Molecular Sequence Data, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, meckel syndrome, 03 medical and health sciences, Model Organisms, Intraflagellar transport, Ciliogenesis, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Animals, Humans, Cilia, Amino Acid Sequence, Caenorhabditis elegans Proteins, Mutation Detection, intraflagellar transport, General Immunology and Microbiology, Organisms, Biology and Life Sciences, Membrane Proteins, Cell Biology, Fibroblasts, biology.organism_classification, Invertebrates, caenorhabditis-elegans, 030104 developmental biology, Biological Tissue, Membrane protein, Genetic Interactions, membrane-proteins, Caenorhabditis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ciliogenesis
Abstract: Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins—including the previously uncharacterised mammalian Tmem80—and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ., The transition zone is a barrier structure required to maintain the dynamic composition and functional integrity of the cilium. This study describes the pathway by which the transition zone is assembled during cilium formation., Author Summary The primary cilium is a structure found in most animal cell types. Much like an antenna, it is responsible for sensing extracellular signals, including light and small molecules, and conveying this information to the receiving cell and respective tissue or organ. At the base of the cilium is the transition zone (TZ), which acts as a “gate” to regulate the entry and exit of ciliary proteins required for signal transduction. Here, we use the nematode Caenorhabditis elegans as a model system to dissect how different proteins within the TZ assemble to form a functional barrier. We find that the TZ protein MKS-5 (Rpgrip1/Rpgrip1L orthologue) forms the foundation for two different assembly pathways involving two distinct modules: Nephronophthisis (NPHP) and Meckel syndrome (MKS). We show that at the base of the MKS module is CEP-290, another TZ protein that assembles MKS module proteins, including a novel TZ protein we identify as TMEM-218. CEP-290 also helps assemble a potentially separate submodule containing TMEM-138 and CDKL-1. Notably, we provide evidence that the MKS module protein TMEM-17 facilitates cilium formation and is disrupted in the human disorder (ciliopathy) Oral-Facial-Digital Syndrome type 6 (OFD6). Together, our findings provide essential insights into the assembly pathway of the ciliary TZ and suggest further connections between the transition zone and human health.
Published: 2016
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3. A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome

Author: Nizon, Mathilde, Henry, Marcia, Michot, Caroline, Baumann, Clarisse, Bazin, Anne, Bessieres, Bettina, Blesson, Sophie, Cordier-Alex, Marie-Pierre, David, Albert, Delahaye-Duriez, Andrée, Delezoide, Anne-Lise, Dieux-Coeslier, Anne, Doco-Fenzy, Martine, Faivre, Laurence, Goldenberg, Alice, Layet, Valérie, Loget, Philippe, Marlin, Sandrine, Martinovic, Jelena, Odent, Sylvie, Pasquier, Laurent, Plessis, Ghislaine, Prieur, Fabienne, Putoux, Audrey, Rio, Marlène, Testard, Hervé, Bonnefont, Jean-Paul, Cormier-Daire, Valérie, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Génétique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Centre Hospitalier René Dubos [Pontoise], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, CHU Grenoble, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, CHRU Tours, Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hôpital Jean Verdier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique, CHU Caen-Hôpital Clémenceau, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Jonchère, Laurent
Subjects: Male, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mouth Mucosa, Facies, Proteins, Cell Cycle Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Sequence Analysis, DNA, NIPBL, Cornelia de Lange syndrome, Phenotype, somatic mosaicism, Facial Asymmetry, De Lange Syndrome, Face, Mutation, Leukocytes, Humans, Female, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Germ-Line Mutation, buccal cells
Abstract: International audience; Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to an heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: 1) intrauterine growth retardation and postnatal short stature, 2) feeding difficulties and/or gastro-oesophageal reflux, 3) microcephaly, 4) intellectual disability and 5) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and three in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for twenty cases which does not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counseling
Published: 2016
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4. The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

Author: Marie-Ange Delrue, Nathalie Golovkine, Annick Toutain, Marie-Jose Gregoire, Christel Thauvin-Robinet, Nicolas Gruchy, Cédric Le Caignec, Emilie Landais, Bruno Delobel, Olivier Tassy, Pascal Sabouraud, Laurence Taine, Caroline Fiquet, Nathalie Leporrier, Agathe Paubel, Dominique Gaillard, Philippe Jonveaux, Nathalie Bednarek, Jacques Motte, Bruno Leheup, Olivier Brichet, Albert David, Didier Lacombe, Martine Doco-Fenzy, Stéphanie Arpin, Mylène Beri, Sylvain Briault, Monique Mozelle-Nivoix, Camille Leroy, Francine Mugneret, Service de Génétique, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Plateforme Régionale de Biologie Innovante, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Service de génétique médicale [CHU Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Génétique Clinique [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-GHICL, Laboratoire de cytogénétique et génétique moléculaire [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Maladies Rares - Génétique et Métabolisme ( MRGM ), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Service de génétique [Tours], Hôpital Bretonneau-CHRU Tours, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, American Memorial Hospital (Reims), Service de génétique [Reims], Service de psychothérapie de l’enfant et l’adolescent [CHU Reims], Université de Reims Champagne-Ardenne ( URCA ), Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Centre Hospitalier Universitaire de Reims (CHU Reims), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies Rares - Génétique et Métabolisme (MRGM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Université de Reims Champagne-Ardenne (URCA), UL, NGERE, Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Adult, Male, Candidate gene, Adolescent, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Chromosome Disorders, Locus (genetics), Biology, Fibrous Dysplasia, Polyostotic, Bioinformatics, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Intellectual Disability, Genetics, medicine, Humans, Child, Genetic Association Studies, Genetics (clinical), 030304 developmental biology, KIF1A, Behavior, Comparative Genomic Hybridization, 0303 health sciences, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, Brachydactyly, Chromosome Mapping, Overweight, Subtelomere, medicine.disease, [SDV] Life Sciences [q-bio], Child, Preschool, Chromosomes, Human, Pair 2, Autism, Female, Chromosome Deletion, 030217 neurology & neurosurgery, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract: International audience; The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable ‘2q37-deletion syndrome’ or Albright’s hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype–phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.
Published: 2012
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5. High prevalence of infectious events in thrombotic thrombocytopenic purpura and genetic relationship with toll-like receptor 9 polymorphisms: experience of the French Thrombotic Microangiopathies Reference Center

Author: Morgand , Marjolaine, Buffet , Marc, Busson , Marc, Loiseau , Pascale, Malot , Sandrine, Amokrane , Kahina, Fortier , Catherine, London , Jonathan, Bonmarchand , Guy, Wynckel , Alain, Provôt , François, Poullin , Pascale, Vanhille , Philippe, Presne , Claire, Bordessoule , Dominique, Girault , Stéphane, Delmas , Yahsou, Hamidou , Mohamed, Mousson , Christiane, Vigneau , Cécile, Lautrette , Alexandre, Pourrat , Jacques, Galicier , Lionel, Azoulay , Elie, Pène , Frédéric, Mira , Jean-Paul, Rondeau , Eric, Ojeda-Uribe , Mario, Charron , Dominique, Maury , Eric, Guidet , Bertrand, Veyradier , Agnès, Tamouza , Ryad, Coppo , Paul, Center , Thrombotic Microangiopathies Reference, Service d'immunologie et hématologies biologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Jean Dausset, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Néphrologie, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche, Service de néphrologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Référence des microangiopathies thrombotiques ( CNR-MAT ), service d'hématologie-CHU Saint-Antoine [APHP], Service d'Hémaphérèse - Médecine Interne, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Service de médecine interne et néphrologie, CH Valenciennes, Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-Hôpital Sud, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de médecine interne [Nantes], Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], Outcomerea Organization, Outcomerea, Unité de Soins Intensifs [Saint-Louis], Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité Médicale de Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Soins Intensifs et Transplantation Rénale, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'Hématologie Biologique [Béclère], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Amiens-Picardie-hôpital Sud, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Fondation FondaMental [Créteil], Epidémiologie des maladies infectieuses et modélisation (ESIM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service d'immunologie et hématologies biologiques [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], AP-HP - Hôpital Antoine Béclère [Clamart], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], CHU Saint-Antoine [APHP], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère
Subjects: Male, Adult, Exacerbation, Immunology, Thrombotic thrombocytopenic purpura, Human leukocyte antigen, 030204 cardiovascular system & hematology, Infections, 03 medical and health sciences, 0302 clinical medicine, Genetic, Risk Factors, hemic and lymphatic diseases, Genotype, medicine, Prevalence, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Prospective Studies, Registries, Polymorphism, Prospective cohort study, Purpura, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, Thrombotic Thrombocytopenic, Purpura, Thrombotic Thrombocytopenic, business.industry, Thrombotic Microangiopathies, Haplotype, Hematology, Middle Aged, medicine.disease, 3. Good health, Haplotypes, Toll-Like Receptor 9, Cohort, Rituximab, Female, France, business, Infection, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030215 immunology, medicine.drug
Abstract: National audience; BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP. STUDY DESIGN AND METHODS: We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded. RESULTS: Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p \textless 0.001). Infections at diagnosis did not impact prognosis and outcome. Thirty-six percent of patients experienced an infectious event during hospitalization, which resulted in more exacerbation of TTP (p = 0.02). Infections were not overrepresented during treatment in patients who received steroids and/or rituximab. Further genetic analysis of toll-like receptor (TLR)-9 functionally relevant polymorphisms revealed that TLR-9 +2848 G and TLR-9 +1174 A genotypes were more frequent in TTP patients than in controls (p = 0.04 and p = 0.026, respectively) and more particularly in patients negative for the Class II human leukocyte antigen system susceptibility allele DRB1*11 (p = 0.001 and p = 0.002, respectively). Haplotypes estimation showed that 1174A-2848G haplotype was significantly more frequent in TTP (p = 0.004), suggesting a primary role for this haplotype variation in conferring a predisposition for acquired TTP. CONCLUSION: Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP.
Published: 2014
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6. Item response theory and factor analysis as a mean to characterize occurrence of response shift in a longitudinal quality of life study in breast cancer patients

Author: Olivier Graesslin, Damien Jolly, Sylvain Causeret, Thierry Conroy, Michel Velten, Francis Guillemin, Franck Bonnetain, Zeinab Hamidou, Amélie Anota, Jean Cuisenier, Mariette Mercier, Caroline Bascoul-Mollevi, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Service de Cancérologie Médicale, Centre Alexis Vautrin ( CAV ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Epidémiologie et Santé Publique, Pôle Recherche - Innovations, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service Chirurgie, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-Institut Mère Enfant, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), This work was supported by a grant from the 'Institut National du Cancer'., BMC, Ed., Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Cancérologie Médicale [Vandoeuvre-les-Nancy], Centre Alexis Vautrin (CAV), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Oncology, medicine.medical_specialty, Psychometrics, Health-related quality of life, Item Response Theory, Breast Neoplasms, Response shift, Logistic regression, Developmental psychology, Correlation, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Quality of life, Multiple correspondence analysis, Surveys and Questionnaires, Internal medicine, Item response theory, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Mastectomy, Principal Component Analysis, Research, Public Health, Environmental and Occupational Health, Longitudinal analysis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, medicine.disease, humanities, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Principal component analysis, Quality of Life, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Factor analysis, Factor Analysis, Statistical, Psychology, Attitude to Health
Abstract: International audience; BACKGROUND: The occurrence of response shift (RS) in longitudinal health-related quality of life (HRQoL) studies, reflecting patient adaptation to disease, has already been demonstrated. Several methods have been developed to detect the three different types of response shift (RS), i.e. recalibration RS, 2) reprioritization RS, and 3) reconceptualization RS. We investigated two complementary methods that characterize the occurrence of RS: factor analysis, comprising Principal Component Analysis (PCA) and Multiple Correspondence Analysis (MCA), and a method of Item Response Theory (IRT). METHODS: Breast cancer patients (n = 381) completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires at baseline, immediately following surgery, and three and six months after surgery, according to the "then-test/post-test" design. Recalibration was explored using MCA and a model of IRT, called the Linear Logistic Model with Relaxed Assumptions (LLRA) using the then-test method. Principal Component Analysis (PCA) was used to explore reconceptualization and reprioritization. RESULTS: MCA highlighted the main profiles of recalibration: patients with high HRQoL level report a slightly worse HRQoL level retrospectively and vice versa. The LLRA model indicated a downward or upward recalibration for each dimension. At six months, the recalibration effect was statistically significant for 11/22 dimensions of the QLQ-C30 and BR23 according to the LLRA model (p ≤ 0.001). Regarding the QLQ-C30, PCA indicated a reprioritization of symptom scales and reconceptualization via an increased correlation between functional scales. CONCLUSIONS: Our findings demonstrate the usefulness of these analyses in characterizing the occurrence of RS. MCA and IRT model had convergent results with then-test method to characterize recalibration component of RS. PCA is an indirect method in investigating the reprioritization and reconceptualization components of RS.
Published: 2014
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7. Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth

Author: Vera M. Kalscheuer, Céline Bonnet, Stefan A. Haas, Pierre Cacciagli, Sébastien Moutton, Emilie Landais, Laurent Villard, Jacques Motte, Ana Medeira, Martine Doco-Fenzy, Heng-Ye Man, Lionel Van Maldergem, Arjan P.M. de Brouwer, Marlène Rio, Christelle Cabrol, Juliette Dupont, Qingming Hou, Laurence Colleaux, Université Bourgogne Franche-Comté ( UBFC ), Boston University [Boston] ( BU ), Human Molecular Genetics, CHU Necker - Enfants Malades [AP-HP], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Génétique, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), Institute of Medical Genetics, Radboud University Medical Center [Nijmegen], Neuroscience Paris Seine ( NPS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Max Planck Institute for Molecular Genetics, Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Génétique Médicale du CHU de Bordeaux, Service de génétique [Reims], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Sciences Po Grenoble - Institut d'études politiques de Grenoble ( IEPG ), Regional Hospital, Boston University [Boston] (BU), Department Human Molecular Genetics [MPIMG Berlin], Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Department of Human Genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, American Memorial Hospital (Reims), and COLLEAUX, Laurence
Subjects: Male, Genetic Linkage, Bioinformatics, MESH: Child Development Disorders, Pervasive, 0302 clinical medicine, Genes, X-Linked, MESH: Child, Intellectual disability, MESH: Sequence Analysis, RNA, MESH: Animals, MESH: Genetic Variation, Child, Cells, Cultured, Genetics (clinical), X-linked recessive inheritance, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Massive parallel sequencing, Brain, Articles, General Medicine, Autism spectrum disorder, MESH: Young Adult, Child, Preschool, Gene Knockdown Techniques, MESH: Cells, Cultured, Adult, Adolescent, Neurite, MESH: Rats, MESH: Genetic Linkage, Context (language use), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, MESH: Intellectual Disability, Young Adult, 03 medical and health sciences, MESH: Brain, Intellectual Disability, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Neurites, medicine, Animals, Humans, Molecular Biology, Loss function, 030304 developmental biology, MESH: Adolescent, MESH: Humans, [ SDV ] Life Sciences [q-bio], Sequence Analysis, RNA, MESH: Child, Preschool, Genetic Variation, MESH: Adult, medicine.disease, MESH: Neurites, MESH: Gene Knockdown Techniques, MESH: Male, Rats, Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory [NCMLS 6], MESH: Genes, X-Linked, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child Development Disorders, Pervasive, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery
Abstract: Item does not contain fulltext Existence of a discrete new X-linked intellectual disability (XLID) syndrome due to KIAA2022 deficiency was questioned by disruption of KIAA2022 by an X-chromosome pericentric inversion in a XLID family we reported in 2004. Three additional families with likely pathogenic KIAA2022 mutations were discovered within the frame of systematic parallel sequencing of familial cases of XLID or in the context of routine array-CGH evaluation of sporadic intellectual deficiency (ID) cases. The c.186delC and c.3597dupA KIAA2022 truncating mutations were identified by X-chromosome exome sequencing, while array CGH discovered a 70 kb microduplication encompassing KIAA2022 exon 1 in the third family. This duplication decreased KIAA2022 mRNA level in patients' lymphocytes by 60%. Detailed clinical examination of all patients, including the two initially reported, indicated moderate-to-severe ID with autistic features, strabismus in all patients, with no specific dysmorphic features other than a round face in infancy and no structural brain abnormalities on magnetic resonance imaging (MRI). Interestingly, the patient with decreased KIAA2022 expression had only mild ID with severe language delay and repetitive behaviors falling in the range of an autism spectrum disorder (ASD). Since little is known about KIAA2022 function, we conducted morphometric studies in cultured rat hippocampal neurons. We found that siRNA-mediated KIAA2022 knockdown resulted in marked impairment in neurite outgrowth including both the dendrites and the axons, suggesting a major role for KIAA2022 in neuron development and brain function.
Published: 2013
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8. Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature

Author: Cottereau , Edouard, Mortemousque , Isabelle, Moizard , Marie-Pierre, Bürglen , Lydie, Lacombe , Didier, Gilbert-Dussardier , Brigitte, Sigaudy , Sabine, Boute , Odile, David , Albert, Faivre , Laurence, Amiel , Jeanne, Robertson , Robert, Viana Ramos , Fabiana, Bieth , Eric, Odent , Sylvie, Demeer , Bénédicte, Mathieu , Michéle, Gaillard , Dominique, Van Maldergem , Lionel, Baujat , Geneviéve, Maystadt , Isabelle, Héron , Delphine, Verloes , Alain, Philip , Nicole, Cormier-Daire , Valérie, Frouté , Marie-Françoise, Pinson , Lucile, Blanchet , Patricia, Sarda , Pierre, Willems , Marjolaine, Jacquinet , Adeline, Ratbi , Ilham, Van Den Ende , Jenneke, Lackmy-Port Lis , Marylin, Goldenberg , Alice, Bonneau , Dominique, Rossignol , Sylvie, Toutain , Annick, Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre de Référence Anomalies du Développement Ouest, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de génétique médicale, CHU Amiens-Picardie, Head of the Department of Medical Genetics, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Regional Hospital, Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence ' Anomalies du Développement et Syndromes Malformatifs Sud - Est PACA ', Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Génétique Médicale et Foetopathologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Génétique Médicale, Département de Génétique médicale, Institut National d'Hygiène, Centre de Génomique Humaine, Université Mohamed V Souissi, Biomedical Sciences, University of Antwerp (UA), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Mohammed V de Rabat [Agdal] (UM5), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagerie et cerveau, Service de Génétique et d'Embryologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Univerity of Antwerp, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-CHRU Tours, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Centre de Référence Anomalies du Développement Ouest, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Heart Defects, Congenital, [SDV.GEN]Life Sciences [q-bio]/Genetics, Arrhythmias, Cardiac, Genetic Diseases, X-Linked, Arrhythmias, X-Linked, Gigantism, Congenital, Phenotype, Glypicans, Genetic Diseases, Intellectual Disability, Mutation, Humans, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Cardiac, Heart Defects
Abstract: International audience; Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked multiple congenital abnormality/intellectual disability syndrome characterized by pre- and post-natal overgrowth, distinctive craniofacial features, macrocephaly, variable congenital malformations, organomegaly, increased risk of tumor and mild/moderate intellectual deficiency. In 1996, Glypican 3 (GPC3) was identified as the major gene causing SGBS but the mutation detection rate was only 28-70%, suggesting either genetic heterogeneity or that some patients could have alternative diagnoses. This was particularly suggested by some reports of atypical cases with more severe prognoses. In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported. In the genetics laboratory in Tours Hospital, GPC3 molecular testing over more than a decade has detected pathogenic mutations in only 8.7% of individuals with SGBS. In addition, GPC4 mutations have not been identified thus raising the question of frequent misdiagnosis. In order to better delineate the phenotypic spectrum of SGBS caused by GPC3 mutations, and to try to define specific clinical criteria for GPC3 molecular testing, we reviewed the clinical features of all male cases with a GPC3 mutation identified in the two molecular laboratories providing this test in France (Tours and Paris). We present here the results of the analysis of 42 patients belonging to 31 families and including five fetuses and three deceased neonates.
Published: 2013
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9. Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

Author: Jean-Bernard Palcoux, Bertrand Guidet, Hanspeter Rottensteiner, Dominique Bordessoule, Didier Gruson, Paul Coppo, Claire Pouteil-Noble, Jacques Pourrat, Jean-Paul Mira, Alain Wynckel, Cécile Vigneau, Agnès Veyradier, Claire Presne, Pierre-Yves Boëlle, Cyrielle Assie, Sandrine Malot, Cédric Daubin, Rana Grillberger, Lionel Galicier, Philippe Vanhille, Marc Buffet, Véronique Le Guern, François Provôt, Gabriel Choukroun, Guy Bonmarchand, Mohamed Hamidou, Christiane Mousson, Ygal Benhamou, Pascale Poullin, Elie Azoulay, Eric Rondeau, Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie et hématologies biologiques [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Baxter Innovations GmbH, Campus Vienna, Service de Néphrologie, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Service d'Hémaphérèse - Médecine Interne, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de néphrologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Réanimation, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin-Tripode, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service de Médecine Interne, Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de réanimation médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de médecine interne et néphrologie, CH Valenciennes, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie pédiatrique, CHU Clermont-Ferrand, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service d'immunologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Etablissement Français du Sang (CS/2002/009), GIS-Institut des Maladies Rares (GIS MR0428)., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de Médecine Interne [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de Référence des microangiopathies thrombotiques ( CNR-MAT ), service d'hématologie-CHU Saint-Antoine [APHP], Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'immunologie et hématologies biologiques, CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche, CHU Amiens-Picardie-Hôpital Sud, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Service de Réanimation Médicale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, De Villemeur, Hervé, and Service d'immunologie et hématologies biologiques [CHU Saint-Antoine]
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, medicine.medical_specialty, Thrombotic thrombocytopenic purpura, ADAMTS13 Protein, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, rituximab, Internal medicine, plasma exchange, medicine, Humans, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Registries, thrombotic thrombocytopenic purpura, prognostic factor, Aged, Purpura, Thrombocytopenic, Idiopathic, Framingham Risk Score, Acquired Thrombotic Thrombocytopenic Purpura, Models, Statistical, business.industry, Reproducibility of Results, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Prognosis, ADAMTS13, 3. Good health, Surgery, ADAM Proteins, ROC Curve, Cohort, Rituximab, Female, Caplacizumab, Original Articles and Brief Reports, business, 030215 immunology, medicine.drug, Cohort study
Abstract: Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death.The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion.Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death.A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.
Published: 2012
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10. Facteurs associés à l'inclusion des patients dans le programme PRADO Insuffisance Cardiaque : étude cas-témoin au Centre Hospitalier de Troyes en 2017–2018

Author: Bourakba, Nadia, Dacunka, Marianne, Marchais, Aurélie, Chapoutot, Laurent, Barbe, Coralie, Hurtaud, Aline, Sanchez, Stéphane, Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Centre Hospitalier de Troyes - Hôpital Simone Veil (CH Troyes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Real Expression Artificial Life (IRIT-REVA), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: suivi à domicile programme, inclusions, managed care, maladie chronique, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, heart failure program, insuffisance cardiaque, chronic disease
Abstract: International audience; ObjectivesIn 2013, the French National Health Insurance set up a programme to help patients with heart failure to return home and stay there (PRADO). During a hospitalization for cardiac decompensation, the medical team decides on the inclusion of the patient in the programme based on eligibility criteria defined. The objective of this study was to identify the factors most associated with the inclusion of heart failure patients in the PRADO program.Materials and MethodsThis was a monocentric retrospective analytical stratified case-control study. It focused on the analysis of patient records hospitalized for cardiac decompensation between 01/01/2017 and 31/12/2018 in the cardiology department of the Centre Hospitalier de Troyes. For each patient included in the PRADO Heart Failure programme, one or two controls, not included in the PRADO Heart Failure programme were matched. The matching was exact without discounting. It was performed on the following criteria: age in 10-year increments, sex, main diagnosis of the stay, major category of diagnosis of the stay and its type (medical or surgical), the severity score of the Homogeneous Group of Patients of the stay and the Charlson score.ResultsA total of 40 patients included in PRADO Heart Failure were matched to 56 controls not included in PRADO Heart Failure. Patients with respiratory disease (3.77 [1.07 – 13.29]), as well as patients on renin-angiotensin system inhibitors (2.24 [1.61 – 5.31]) were more often included in the PRADO Heart Failure programme. The most frequent criteria for non-eligibility were the need to transfer the patient to a specialised institution and significant impairment of higher functions.ConclusionRespiratory comorbidity and renin-angiotensin system blocker treatment are the factors most associated with the inclusion of heart failure patients in the PRADO Heart Failure programme.; Objectifs : En 2013, l'Assurance Maladie a mis en place un "Programme d'aide au retour et maintien à domicile (PRADO)" pour les patients insuffisants cardiaques. Au cours d'une hospitalisation pour décompensation cardiaque, l’équipe médicale décide de l'inclusion du patient dans le programme en se basant sur des critères d’éligibilité définis par l'Assurance Maladie. L'objectif de cette étude était d'identifier les facteurs les plus associés à l'inclusion des patients insuffisants cardiaques dans le programme PRADO Insuffisance Cardiaque. Matériels et méthodes : Il s'agissait d'une étude cas-témoins rétrospective analytique monocentrique. Elle portait sur l'analyse de dossiers patients hospitalisés pour décompensation cardiaque entre le 01/01/2017 et le 31/12/2018 dans le service de cardiologie du Centre Hospitalier de Troyes. Pour chaque patient inclus dans le programme PRADO Insuffisance Cardiaque, un ou deux témoins, non inclus dans le programme PRADO Insuffisance Cardiaque ont été appariés. L'appariement était exact sans remise. Il a été réalisé sur les critères suivants : l’âge par tranches de 10 ans, le sexe, le diagnostic principal du séjour, la catégorie majeure de diagnostic du séjour et son type (médical ou chirurgical), le score de sévérité du Groupe homogène de malades du séjour et le score de Charlson. Résultats : Au total, 40 patients inclus dans le PRADO Insuffisance Cardiaque ont été appariés à 56 témoins non inclus dans le PRADO Insuffisance Cardiaque. Les patients présentant une pathologie respiratoire (3,77 [1,07 – 13,29]), ainsi que les patients sous inhibiteurs du système rénine-angiotensine (2,24 [1,61 – 5,31]) étaient plus souvent inclus dans le programme PRADO Insuffisance Cardiaque. Les critères de non-éligibilité les plus fréquents étaient la nécessité de transférer le patient vers une institution spécialisée et l'altération significative des fonctions supérieures.
Published: 2022
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11. The role of circumstances of diagnosis and access to dermatological care in early diagnosis of cutaneous melanoma: a population-based study in France

Author: Dan Lipsker, Catherine Michel, Florence Granel-Brocard, Arlette Danzon, François Truchetet, Stéphane Dalle, Philippe Bernard, G. Reuter, G. Hedelin, Fabien Vitry, Frédérique Durbec, Beatrice Domissy-Baury, Marie-Laure Batard, Jean-Michel Halna, François Aubin, Florent Grange, Sophie Dalac, Christian Delvincourt, Jean Luc Schmutz, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Registre des cancers du Bas-Rhin, CRLCC Paul Strauss, Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Direction de la recherche, Société des accumulateurs fixes et de traction ( SAFT ), Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de l'Hôtel Dieu [CHU-HCL], Hospices Civils de Lyon (HCL), and Société des accumulateurs fixes et de traction (SAFT)
Subjects: Male, Skin Neoplasms, Time Factors, MESH : Retrospective Studies, MESH : Aged, Health Services Accessibility, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH : Health Services Accessibility, MESH: Risk Factors, Risk Factors, Surveys and Questionnaires, Medicine, MESH : Neoplasm Staging, MESH : Female, MESH: Incidence, skin and connective tissue diseases, Melanoma, ComputingMilieux_MISCELLANEOUS, MESH: Aged, education.field_of_study, MESH: Health Services Accessibility, MESH: Middle Aged, Incidence (epidemiology), Incidence, MESH : Questionnaires, General Medicine, MESH: Neoplasm Staging, MESH: Follow-Up Studies, Middle Aged, MESH : Adult, MESH : Risk Factors, MESH : Incidence, 3. Good health, 030220 oncology & carcinogenesis, MESH : Dermatology, Female, MESH: Clinical Competence, Clinical Competence, France, MESH : Time Factors, Adult, medicine.medical_specialty, MESH: Melanoma, MESH : Male, Population, MESH : Melanoma, MESH: Dermatology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Breslow Thickness, 03 medical and health sciences, Nevus, Humans, MESH : Middle Aged, Lentigo maligna melanoma, education, MESH : France, Aged, Neoplasm Staging, Retrospective Studies, MESH: Humans, business.industry, MESH: Questionnaires, MESH: Skin Neoplasms, MESH: Time Factors, MESH : Skin Neoplasms, MESH : Humans, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, MESH : Follow-Up Studies, medicine.disease, MESH : Clinical Competence, MESH: Male, Superficial spreading melanoma, MESH: France, Cutaneous melanoma, business, MESH: Female, Follow-Up Studies
Abstract: International audience; OBJECTIVES: To describe circumstances of the diagnosis and access to dermatological care for patients with cutaneous melanoma (CM) and to investigate factors associated with early detection. DESIGN: Retrospective population-based study of incident cases of invasive CM in 2004, using questionnaires to physicians and a survey of cancer registries and pathology laboratories. SETTING: Five regions in northeastern France. PATIENTS: Six hundred fifty-two patients who were referred to dermatologists by general practitioners (group 1) or by other specialists (group 2), who directly consulted a dermatologist for CM (group 3), or who were diagnosed as having CM during a prospective follow-up of nevi (group 4) or when consulting a dermatologist for other diseases (group 5). MAIN OUTCOME MEASURES: Characteristics of patients, tumors, and patients' residence in each group, including the geographical concentration of dermatologists. We performed multivariate analysis of these factors to determine association with Breslow thickness. RESULTS: Age, tumor location, Breslow thickness, ulceration, histological type, and geographical concentration of dermatologists significantly differed among groups. Patients consulting dermatologists directly formed the largest group (45.1%). Those referred by general practitioners (26.1%) were the oldest and had the highest frequency of thick (>3 mm), nodular, and/or ulcerated CM. Patients from groups 4 (8.4%) and 5 (14.1%) had the thinnest CMs. Ulcerated and/or thick tumors were absent in group 4. In multivariate analysis, histological types superficial spreading melanoma and lentigo maligna melanoma, younger age, high concentration of dermatologists, and detection by dermatologists were significantly associated with thinner CMs. CONCLUSION: Easy access of patients to dermatologists, information campaigns targeting elderly people, and education of general practitioners are complementary approaches to improving early detection.
Published: 2010
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12. Genotype-phenotype correlation in four 15q24 deleted patients identified by array-CGH

Author: Bruno Delobel, Emilie Landais, Tania Attié-Bitach, Martine Doco-Fenzy, ElÃ©onore Blondeel, MarlÃ¨ne Rio, Joris Andrieux, Elsa Delaby, ChristÃ¨le Dubourg, Sylvie Manouvrier-Hanu, Muriel Holder-Espinasse, Henri Copin, Hubert Journel, Sylvie Odent, MichÃ¨le Mathieu, Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Moléculaire et Hormonologie, Hôpital Pontchaillou, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie-Génétique, CHU Amiens-Picardie-Hôpital nord, Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Laboratoire de Cytogénétique, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-GHICL, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), De Villemeur, Hervé, Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Bretagne Atlantique-Hôpital Chubert, Université de Picardie Jules Verne ( UPJV ) -CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), and Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )
Subjects: Male, Pathology, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, MESH: Genotype, 0302 clinical medicine, MESH: Pregnancy, MESH : Child, Pregnancy, MESH: Child, Genotype, MESH : Female, Child, MESH : Comparative Genomic Hybridization, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), Genetics, 0303 health sciences, Comparative Genomic Hybridization, MESH: Infant, Newborn, Long philtrum, MESH : Infant, Chromosome Breakage, Micropenis, MESH : Chromosomes, Human, Pair 15, MESH: Infant, 3. Good health, MESH : Phenotype, Phenotype, MESH: Chromosome Breakage, Child, Preschool, Female, Chromosome breakage, Chromosome Deletion, Haploinsufficiency, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, MESH : Male, MESH: Chromosome Deletion, 15q24 deletion, Biology, genotype-phenotype correlation, MESH : Infant, Newborn, MESH: Phenotype, Article, 03 medical and health sciences, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Chromosomes, Human, Pair 15, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, Newborn, Infant, medicine.disease, MESH : Chromosome Deletion, Iris coloboma, MESH: Male, MESH: Comparative Genomic Hybridization, MESH : Pregnancy, Palpebral fissure, MESH : Chromosome Breakage, Hypospadias, array-CGH, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, 030217 neurology & neurosurgery, MESH: Chromosomes, Human, Pair 15
Abstract: International audience; Microdeletion 15q24 is an emerging syndrome recently described, mainly due to increased use of array-CGH. Clinical features associate mild to moderate developmental delay, typical facial characteristics (high forehead and frontal hairline, broad eyebrows, downslanting palpebral features, long philtrum), hands (particularly proximal implanted thumbs) and genital anomalies (micropenis, hypospadias). We report here on four de novo cases having 2.5-6.1 Mb deletions involving 15q24: one 15q23q24.2 (Patient 1) and three 15q24.1q24.2 deletions (Patients 2-4). We correlate phenotype to genotype according to molecular boundaries of these deletions. Since bilateral iris coloboma and severe ano-rectal malformation were only present in Patient 1, we could link these anomalies to haploinsufficiency of 15q23 genes. Neither hypospadias nor micropenis were present in Patient 3 bearing the smallest deletion, therefore we could define 500 kb 15q24.1 region linked to these anomalies.
Published: 2009
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13. Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France

Author: Fabien Vitry, Catherine Lejeune, Patrick Arveux, Kazem Alzahouri, Francis Guillemin, Cédric Baumann, Marie-Christine Woronoff-Lemsi, Michel Velten, Damien Jolly, Nicolas Jay, Irawati Lemonnier, Risques, maladies chroniques et société : des systèmes biologiques aux populations, Université Henri Poincaré - Nancy 1 ( UHP ), Knowledge representation, reasonning ( ORPAILLEUR ), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université Henri Poincaré - Nancy 1 ( UHP ) -Université Nancy 2-Institut National Polytechnique de Lorraine ( INPL ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Henri Poincaré - Nancy 1 ( UHP ) -Université Nancy 2-Institut National Polytechnique de Lorraine ( INPL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), FRANCIM, Réseau des registres français du cancer, Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche, Centre d'Epidémiologie Clinique ( CIC-EC ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Henri Poincaré - Nancy 1 (UHP), Knowledge representation, reasonning (ORPAILLEUR), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: Male, Cancer Research, Complete data, Multivariate analysis, Time Factors, Population level, MESH : Aged, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, MESH : Female, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Disease Management, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Positron-Emission Tomography, MESH: Solitary Pulmonary Nodule, 3. Good health, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Cancer management, Female, Radiology, France, MESH : Solitary Pulmonary Nodule, medicine.symptom, Research Article, MESH : Time Factors, medicine.medical_specialty, MESH : Male, MESH: Disease Management, lcsh:RC254-282, 03 medical and health sciences, Genetics, medicine, Humans, MESH : Middle Aged, MESH : France, Aged, Solitary pulmonary nodule, MESH: Humans, business.industry, MESH: Time Factors, MESH : Humans, Solitary Pulmonary Nodule, MESH : Positron-Emission Tomography, Nodule (medicine), medicine.disease, MESH: Male, MESH : Disease Management, MESH: France, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Positron-Emission Tomography, Observational study, business, MESH: Female
Abstract: Background Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. Methods In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002–2003, and 20,075 in an after-PET period, 2004–2005. Patients were followed through their physician, who was responsible for diagnostic management. Results We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. Conclusion In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches.
Published: 2009
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14. Variations in management of stage I to stage III cutaneous melanoma: a population-based study of clinical practices in France

Author: G. Hedelin, Marie-Laure Batard, Jean-Michel Halna, Catherine Michel, Christian Delvincourt, G. Reuter, Florence Granel-Brocard, Sophie Dalac, Florent Grange, Arlette Danzon, François Truchetet, Jean Luc Schmutz, François Aubin, P. Bernard, Fabien Vitry, Béatrice Baury, Dan Lipsker, Stéphane Dalle, Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Registre des cancers du Bas-Rhin, CRLCC Paul Strauss, Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital de l'Hôtel Dieu [CHU-HCL], and Hospices Civils de Lyon (HCL)
Subjects: Male, Skin Neoplasms, Time Factors, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH: Dose-Response Relationship, Drug, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Interferons, MESH : Population Surveillance, MESH: Interferons, MESH : Neoplasm Staging, MESH : Female, Stage (cooking), Melanoma, ComputingMilieux_MISCELLANEOUS, MESH : Sentinel Lymph Node Biopsy, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH: Middle Aged, MESH : Chemotherapy, Adjuvant, General Medicine, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, 3. Good health, MESH : Antineoplastic Agents, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Population Surveillance, MESH : Dermatology, Female, Radiology, France, MESH : Time Factors, Adult, medicine.medical_specialty, Adolescent, MESH: Melanoma, MESH: Sentinel Lymph Node Biopsy, MESH : Male, Population, Sentinel lymph node, MESH : Melanoma, Antineoplastic Agents, MESH: Dermatology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, MESH: Population Surveillance, Breslow Thickness, 03 medical and health sciences, MESH : Adolescent, Adjuvant therapy, medicine, Humans, MESH : Middle Aged, education, MESH : Aged, 80 and over, MESH : France, Cancer staging, Aged, Neoplasm Staging, Retrospective Studies, MESH: Adolescent, MESH: Humans, Dose-Response Relationship, Drug, business.industry, Sentinel Lymph Node Biopsy, MESH: Skin Neoplasms, MESH: Time Factors, MESH : Humans, MESH : Skin Neoplasms, MESH: Adult, MESH: Retrospective Studies, MESH: Male, Surgery, MESH: France, Regimen, MESH: Antineoplastic Agents, Lymphadenectomy, Interferons, business, MESH: Female
Abstract: International audience; OBJECTIVE: To describe current management of cutaneous melanoma (CM) and identify factors accounting for disparities. DESIGN: Retrospective population-based study using survey of cancer registries and pathology laboratories, and questionnaires to physicians. SETTING: Five regions covering 19.2% of the French territory and including 8.2 million inhabitants. PATIENTS: Incident cases of patients with stage I to stage II (hereinafter, stage I-II) tumors staged according to the American Joint Committee on Cancer Staging guidelines and nodal stage III CM in 2004. MAIN OUTCOME MEASURES: Modalities of diagnosis and excision, surgical margins, sentinel lymph node biopsy, adjuvant therapies and surveillance procedures, and their variations according to age, sex, residence, location of primary CM, Breslow thickness, type of physicians, modalities of decisions, and health care patterns. RESULTS: Clinical stage I-II CMs (n = 710 cases) slightly predominated in females (53%), with a lower mean Breslow thickness (1.4 mm) than in males (1.9 mm). Initial excisions were most often performed by private dermatologists and wide excisions by surgeons. Narrow margins (8%) were associated with advanced age, higher Breslow thickness, and head location. Sentinel lymph node biopsy was performed in 34% of CMs thicker than 1.0 mm, depending on geographical regions, distance from reference centers, and health care patterns. Adjuvant therapies (mainly low-dose interferon) were proposed in 53% of thick CMs (>1.5 mm), depending on the patient's age and geographical region. In contrast with French recommendations, surveillance procedures frequently included systematic medical imaging. Stage III nodal CMs (n = 89 cases) predominated in males (62%). After lymphadenectomy, adjuvant therapies (including high-dose interferon in 32% of cases and chemotherapies in 24% of cases) were proposed in 68% of cases, depending on the patient's age and geographical region. A complete 1-year high-dose interferon regimen was administered in less than 10% of cases. CONCLUSION: Large disparities still exist in the management of CM in France, depending to a greater extent on medical and geographical environment than on the characteristics of either patients or tumors.
Published: 2008
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15. Fast Stent Retrieval during Mechanical Thrombectomy Improves Recanalization in Patients with the Negative Susceptibility Vessel Sign

Author: Sébastien Soize, Laurent Pierot, J.-B. Eymard, Emmanuel Touzé, M. Sahnoun, Pierre-François Manceau, C. Gelmini, S. Cheikh-Rouhou, M. Zuber, Matthias Gawlitza, Département de Neuroradiologie [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, medicine.medical_specialty, Brain Ischemia, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occlusion, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Stent retrieval, Adverse effect, Aged, Thrombectomy, Aged, 80 and over, Interventional, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Confidence interval, 3. Good health, Stroke, Mechanical thrombectomy, Treatment Outcome, Relative risk, Cardiology, Female, Stents, Neurology (clinical), business, 030217 neurology & neurosurgery, Sign (mathematics)
Abstract: BACKGROUND AND PURPOSE: In acute ischemic stroke, the negative susceptibility vessel sign on T2*-weighted images traditionally highlights fibrin-rich clots, which are particularly challenging to remove. In vitro, fast stent retrieval improves fibrin-rich clot extraction. We aimed to evaluate whether the speed of stent retrieval influences the recanalization and clinical outcome of patients presenting with the negative susceptibility vessel sign. MATERIALS AND METHODS: Patients were identified from a registry of patients with ischemic stroke receiving mechanical thrombectomy between January 2016 and January 2020. Inclusion criteria were the following: 1) acute ischemic stroke caused by an isolated occlusion of the anterior circulation involving the MCA (Internal Carotid Artery-L, M1, M2) within 8 hours of symptom onset; 2) a negative susceptibility vessel sign on prethrombectomy T2*-weighted images; and 3) treatment with a combined technique (stent retriever + contact aspiration). Patients were dichotomized according to retrieval speed (fast versus slow). The primary outcome was the first-pass recanalization rate. RESULTS: Of 68 patients who met inclusion criteria, 31 (45.6%) were treated with fast retrieval. Patients receiving a fast retrieval had greater odds of first-pass complete (relative risk and 95% confidence interval [RR 95% CI], 4.30 [1.80–10.24]), near-complete (RR 95% CI, 3.24 [1.57–6.68]), and successful (RR 95% CI, 2.60 [1.53–4.43]) recanalization as well as greater odds of final complete (RR 95% CI, 4.18 [1.93–9.04]), near-complete (RR 95% CI, 2.75 [1.55–4.85]), and successful (RR 95% CI, 1.52 [1.14–2.03]) recanalization. No significant statistical differences in procedure-related serious adverse events, distal embolization, or symptomatic intracranial hemorrhage were reported. No differences were noted in terms of functional independence (RR 95% CI, 1.01 [0.53–1.93]) and all-cause mortality (RR 95% CI, 0.90 [0.35–2.30]) at 90 days. CONCLUSIONS: A fast stent retrieval during mechanical thrombectomy is safe and improves the retrieval of clots with the negative susceptibility vessel sign.
Published: 2021
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16. Clinical and Organizational Impacts of Medical Ordering Settings on Patient Pathway and Community Pharmacy Dispensing Process: The Prospective ORDHOSPIVILLE Study

Author: Justine Clarenne, Julien Gravoulet, Virginie Chopard, Julia Rouge, Amélie Lestrille, François Dupuis, Léa Aubert, Sophie Malblanc, Coralie Barbe, Florian Slimano, Céline Mongaret, Faculty of pharmacy, Centre Hospitalier Universitaire de Reims (CHU Reims), Faculté de Pharmacie [Nancy], Université de Lorraine (UL), Pharmacie Gravoulet, Observatoire du Médicament, des Dispositifs médicaux et de l'Innovation Thérapeutique Grand Est, Faculty of Pharmacy, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Agence Régionale de Santé Grand-Est (ARS Grand-Est), Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, and Université de Reims Champagne-Ardenne (URCA)
Subjects: [PHYS]Physics [physics], community pharmacist, [SDV]Life Sciences [q-bio], pharmacist intervention, 030226 pharmacology & pharmacy, organizational impact, Article, drug-related problems, 3. Good health, hospital discharge, 03 medical and health sciences, 0302 clinical medicine, [CHIM]Chemical Sciences, Pharmacology (medical), 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, clinical impact
Abstract: International audience; During the dispensing process of medical orders (MOs), community pharmacists (CPs) can manage drug-related problems (DRPs) by performing pharmacist interventions (PIs). There is little evidence that the PI rate is higher with MOs from hospitals (MOHs) than ambulatory (MOAs) settings, and their impact on the patient and community pharmacy is unknown. The primary objective of this study was to compare the MOH and MOA PI rates. The secondary objective was to describe PIs and their clinical and organizational impacts on patient and community pharmacy workflow. A total of 120 CPs participated in a prospective study. Each CP included 10 MOH and 10 MOA between January and June 2020. DRP and PI description and clinical and organizational impacts between MOH and MOA were assessed and compared. We analyzed 2325 MOs. PIs were significantly more frequent in MOH than in MOA (9.7% versus 4.7%; p < 0.001). The most reported PI was the difficulty of contacting hospital prescribers (n = 45; 52.2%). MOHs were associated with a longer dispensing process time and a greater impact on patient pathway and community pharmacy workflow than MOAs. Lack of communication between hospital and primary care settings partly explains the results. Implementation of clinical pharmacy activities at patient discharge could alleviate these impacts.
Published: 2022
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17. A pilot study of procoagulant platelet extracellular vesicles and P-selectin increase during induction treatment in acute lymphoblastic leukaemia paediatric patients: two new biomarkers of thrombogenic risk?

Author: Philippe Nguyen, Sandra Audonnet, Claire Pluchart, Gael Poitevin, Coralie Barbe, Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Département d'hémato-oncologie pédiatrique [Hôpital American Memorial, Reims], Hôpital American Memorial [Reims], Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Plateau Technique de Cytométrie en Flux (URCACyt), Service d'hématologie [Reims], Hôpital Robert Debré, and Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Platelets, Blood Platelets, Male, medicine.medical_specialty, P-selectin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Pilot Projects, 030204 cardiovascular system & hematology, Extracellular vesicles, 03 medical and health sciences, Extracellular Vesicles, Leukocyte Count, 0302 clinical medicine, Internal medicine, Medicine, Asparaginase, Humans, Platelet, 030212 general & internal medicine, Platelet activation, Child, Correlation of Data, Blood Coagulation, Paediatric patients, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Hematology, Venous thromboembolism, business.industry, Platelet Count, Acute lymphoblastic leukaemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Induction Chemotherapy, Venous Thromboembolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Platelet Activation, Thrombosis, 3. Good health, P-Selectin, Immunology, Biomarker (medicine), Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: International audience; In paediatric acute lymphoblastic leukaemia (ALL), focus has shifted towards preventing treatment-related complications, including venous thromboembolism, the cause of significant mortality and morbidity. To better understand thrombogenic mechanisms during induction treatment, we studied the number, origin and procoagulant activity of extracellular vesicles (EVs) and P-selectin level throughout the induction course in 24 paediatric patients. EVs were mainly of platelet origin. We observed a significant increase in EV number, in platelet EV number and P-selectin level throughout the induction course. There was a correlation between higher EV and platelet EV number, P-selectin level, higher platelet count and leucocyte count. We also observed a correlation between higher EV procoagulant activity and higher platelet count and leucocyte count and higher P-selectin level. Older age and T phenotype were associated with a higher EV procoagulant activity. Platelet EV generation may play a role in thrombogenic complications in ALL patients and could serve as a biomarker to identify patients with a high risk of thrombosis. As a marker of platelet activation, P-selectin may be another relevant marker with the advantage of being easier to analyse in clinical practice.
Published: 2020
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18. Efficacy of eculizumab in refractory life-threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia

Author: Anne Quinquenel, Maxime Hentzien, Alain Delmer, Alain Wynckel, Anne-Cécile Gauchy, Cyrielle Rodier, Victoire de Marcellus, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Service de Néphrologie, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Service d'Hématologie Clinique [CHU Reims], and Hôpital universitaire Robert Debré [Reims]
Subjects: Medicine (General), chronic myelomonocytic leukemia, Chronic myelomonocytic leukemia, Case Report, Case Reports, 030204 cardiovascular system & hematology, 03 medical and health sciences, R5-920, 0302 clinical medicine, Refractory, hemic and lymphatic diseases, medicine, Direct antiglobulin test, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Eculizumab, medicine.disease, 3. Good health, warm autoimmune hemolytic anemia, 030220 oncology & carcinogenesis, Immunology, Medicine, eculizumab, Autoimmune hemolytic anemia, business, medicine.drug
Abstract: Eculizumab may be considered as an emergency therapeutic option in refractory life‐threatening warm autoimmune hemolytic anemia especially if direct antiglobulin test is positive for both IgG and C3d and after failure of all conventional treatments.
Published: 2020
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19. Pressure-Driven Gas Flows in Micro Channels with a Slip Boundary: A Numerical Investigation

Author: F. Mebarek-Oudina, R. Fares, A. Zaim, M. Sahnoun, L. Kolsi, Abderrahmane Aissa, M. E. Ganaoui, Mohamed El-Amine Slimani, United Arab Emirates University, Laboratoire de Physique des Matériaux et Modélisation des Systèmes [Meknès] (LP2MS), Université Moulay Ismail (UMI), University of Hail, Département de Neuroradiologie [CHU Reims], and Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche
Subjects: [SPI]Engineering Sciences [physics], Materials science, General Materials Science, Mechanics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020
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20. Patterns of recurrence and prognosis in locally advanced FIGO stage IB2 to IIB cervical cancer: Retrospective multicentre study from the FRANCOGYN group

Author: Xavier Carcopino, Cyril Touboul, Marcos Ballester, Emilie Raimond, Pierre Collinet, Vincent Lavoué, Olivier Graesslin, Cyrille Huchon, Alexandre Bricou, Geoffroy Canlorbe, Emile Daraï, J. Varinot, Marie-Emmanuelle Neveu, Tiphaine de Foucher, L. Monnier, Lobna Ouldamer, Sofiane Bendifallah, Service de Gynécologie-Obstétrique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre de Recherche Saint-Antoine (CR Saint-Antoine), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition, croissance et cancer (U 1069) (N2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de Pathologie [CHU Tenon], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de gynécologie-obstétrique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Bretonneau, Hôpitaux Universitaires de Paris Seine-Saint-Denis, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Institut de Recherche pour le Développement (IRD) Marseille (IRD Marseille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Jeanne de Flandre [Lille], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Thérapies Laser Assistées par l'Image pour l'Oncologie (ONCO-THAI), and Service de gynécologie et obstétrique [Poissy - Saint-Germain-en-Laye]]
Subjects: Oncology, Survival, medicine.medical_treatment, Brachytherapy, Uterine Cervical Neoplasms, 0302 clinical medicine, Recurrence, Cumulative incidence, Stage (cooking), Lymph node, Peritoneal Neoplasms, Cervical cancer, Aged, 80 and over, 030219 obstetrics & reproductive medicine, General Medicine, Chemoradiotherapy, Middle Aged, 3. Good health, Survival Rate, medicine.anatomical_structure, Time to recurrence, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Vagina, Female, Adult, medicine.medical_specialty, Locally advanced, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Hysterectomy, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Retrospective Studies, Locally advanced cervical cancer, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, Pattern, medicine.disease, Concomitant, Surgery, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Introduction Evidence-based data describing patterns of recurrence and prognosis in women with FIGO stage IB2 to IIB locally advanced cervical cancer (LACC) are scarce. The purpose of this study was to analyse patterns of recurrence in LACC and their correlation with prognosis, depending on FIGO stage, lymph node (LN) status and treatment modalities. The endpoints of this study were the type of recurrence (locoregional or distant, and time to recurrence), the recurrence free survival, the overall survival and the cumulative incidence for both locoregional and distant recurrence. Materials and methods Data of women with FIGO stage IB2 to IIB CC treated between April 1996 and May 2016 were retrospectively abstracted from nine French institutions. Results The median follow-up for the 501 women included was 35.6 months. Recurrences were observed in 158 (31.5%), with a mean time to recurrence of 20.7 months. Women with IIB CC had poorer prognosis, lower 3-year RFS and higher 3-year cumulative incidence of both locoregional and distant recurrences. Women with positive or unknown LN status had poorer prognosis with higher 3-year cumulative incidence of distant recurrence. Women who underwent concomitant chemo-radiotherapy ± vaginal brachytherapy had poorer prognosis, with lower 3-year RFS and higher 3-year cumulative incidence of distant recurrence. Conclusions Recurrence location and time to recurrence differ widely depending on the FIGO stage, LN status and treatment modalities, with potential impact on follow-up modalities and therapeutic approaches.
Published: 2019
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21. Caractérisation phénotypique et génomique des patients Becker avec délétion des exons 45-55

Author: Gargaun, Elena, Yaou, Rabah Ben, Solé, Guilhem, Tiffreau, Vincent, Laforet, Pascale, Parent, Michel, Bassez, Guillaume, Stojkovic, Tanya, Vanhulle, Catherine, Servais, Laurent, Lacombe, Pascal, Pedespan, Jean-Michel, Kettaneh, Adrien, Roche, Corinne, Gaillard, Dominique, Sacconi, Sabrina, Faivre, Laurence, Nadaj-Pakleza, Alexandra, Vallat, Jean Michel, Laroche, Cécile, Moing, Anne-Gaëlle Le, Durigneux, Julien, Themar-Noel, Christine, Negrier, Marie Laure, Espil-Taris, Caroline, Boucher, Elise, Delaubier, Anne, Guillou, Claire, Cuisset, Jean Marie, Urtizberea, Andoni, Eymard, Bruno, Boland, Anne, Deleuze, Jean François, Salgado, David, Krahn, Martin, Levy, Nicolas, Blesius, Alexia, Leturcq, France, Pietri-Rouxel, France, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Activité Physique, Muscle, Santé (EA4488), Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service of Clinical Trials and Databases, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux Ségalen [Bordeaux 2], Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Vichy], CH Vichy, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), CHU Nice, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institute of Developmental Biology and Cancer (IBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Neurologie [CHU Limoges], CHU Limoges, Service de Pédiatrie médicale [CHU Limoges], Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 87, avenue Raymond-Poincaré, 75116 Paris, parent, University Hospital, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Bordeaux (UB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Biochimie et Génétique Moléculaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP]
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; La dystrophie musculaire de Becker (BMD) est une pathologie liée à l’X qui se caractérise par une dégénérescence des muscles squelettiques et/ou associée à une cardiomyopathie. Les patients Becker BMDdel45-55 présentent une délétion “en phase” des exons 45 à 55 dans le gène DMD. Les introns 44 et 55 qui bordent cette délétion contiennent des séquences régulatrices comme des long-non-coding ARN (lncRNA). Chaque patient BMDdel45-55 présente un point de cassure différent et donc un neo-intron unique avec potentiellement des modifications dans les séquences de lncRNA.L’objectif du projet est d’établir une caractérisation génomique d’une cohorte unique de patients BMDdel45-55 et d’étudier des facteurs impliqués dans leur variabilité phénotypique.Nous avons réalisé (i)une caractérisation phénotypique chez 49 patients, (ii)un séquençage du génome entier chez 19/49 patients et (iii)une étude des lncRNA chez 38/49 patients. Nous avons établi le profil des lncRNA dans des myoblastes immortalisés des sujets sains et DMD avec une délétion des exons 45-52 (Myo-45-52).L’étude phénotypique de notre population identifie une cardiomyopathie dilatée (22%), des difficultés à la marche/course (46%), la fatigabilité (34%). Dans 51% l’âge d’apparition des premiers signes est
Published: 2019

22. A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Author: François Vialard, Eva Pipiras, Pascale Kleinfinger, Dominique Martin-Coignard, Marie Catty, Elisabeth Flori, Emilie Landais, Mylène Valduga, Marie-France Portnoï, Aline Receveur, Agnès Choiset, Ghislaine Plessis, Nathalie Le Meur, Audrey Basinko, Justine Besseau-Ayasse, James Lespinasse, Radu Harbuz, Céline Poirsier, Martine Doco-Fenzy, Pascaline Letard, Caroline Schluth-Bolard, Anne Bazin, Jérôme Toutain, Fabienne Prieur, Florence Amblard, Cédric Le Caignec, Tiffany Busa, Marie Christine de Blois, Melanie Jimenez, Patrick Callier, Chantal Missirian, Céline Pebrel-Richard, Paul Kuentz, Catherine Yardin, François Cartault, Hakima Lallaoui, Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), UVSQ - Département de maïeutique (UVSQ Maïeutique), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de cytogénétique et génétique moléculaire [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Service de génétique, Centre hospitalier Félix Guyon, Bellepierre, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Laboratoire de génétique médicale et cytogénétique [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), CHU Clermont-Ferrand, Service de Génétique et d'Embryologie Médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service d'histologie, embryologie et cytogénétique [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-Hôpital Couple-Enfant, Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Activité Motrice et Adaptation PsychoPhysiologique (AMAPP), Université d'Orléans (UO), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service Histologie-embryologie-cytogénétique, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire Pasteur Cerba, Laboratoire de Cytogénétique, CHI Poissy-Saint-Germain, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Laboratoire CERBA [Saint Ouen l'Aumône], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Association des Cytogénéticiens de Langue Française, Gamètes, implantation, gestation (GIG), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Institut Pasteur [Paris]-Laboratoire CERBA [Saint Ouen l'Aumône], Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy]
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, 22q11 Deletion Syndrome, Adolescent, [SDV]Life Sciences [q-bio], Population, Article, 03 medical and health sciences, Intellectual disability, Genetics, medicine, Humans, Genetic Testing, Child, education, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, Fluorescence, Genetics (clinical), Comparative Genomic Hybridization, Fetus, education.field_of_study, business.industry, Incidence (epidemiology), Infant, Newborn, Cytogenetics, Infant, Microdeletion syndrome, medicine.disease, 3. Good health, 030104 developmental biology, Child, Preschool, Cohort, Paternal Inheritance, Female, France, business, Comparative genomic hybridization
Abstract: Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.
Published: 2015
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23. Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability

Author: Létard, Pascaline, Drunat, Séverine, Vial, Yoann, Duerinckx, Sarah, Ernault, Anais, Amram, Daniel, Arpin, Stéphanie, Bertoli, Marta, Busa, Tiffany, Ceulemans, Berten, Desir, Julie, Doco-Fenzy, Martine, Elalaoui, Siham Chafai, Devriendt, Koenraad, Faivre, Laurence, Francannet, Christine, Geneviève, Geneviève, Gitiaux, Cyril, Julia, Sophie, Lebon, Sébastien, Lubala, Toni, Mathieu-Dramard, Michèle, Maurey, Hélène, Metreau, Julia, Nasserereddine, Sanaa, Nizon, Mathilde, Pierquin, Geneviève, Pouvreau, Nathalie, Rivier-Ringenbach, Clothilde, Rossi, Massimiliano, Schaefer, Elise, Sznajer, Yves, Tunca, Yusuf, Guilmin Crepon, Sophie, Alberti, Corinne, Elmaleh-Bergès, Monique, Benzacken, Brigitte, Wollnick, Bernd, Woods, C Geoffrey, Rauch, Anita, El Ghouzzi, Vincent, Gressens, Pierre, Verloes, Alain, Passemard, Sandrine, Geneviève, David, Julia, Julia, Woods, C. Geoffrey, Mordel, S, Schaeffer, Stéphane, Dupas, S., Laville, Marie-Alice, Chapon, Françoise, Allouche, S., Mordel, Patrick, Dupas, Quentin, Reggiani, Claudio, Coppens, Sandra, Sekhara, Tayeb, Dimov, Ivan, Pichon, Bruno, Lufin, Nicolas, Addor, Marie-Claude, Belligni, Elga Fabia, Digilio, Maria Cristina, Faletra, Flavio, Ferrero, Giovanni Battista, Gérard, Marion, Isidor, Bertrand, Joss, Shelagh, Niel-Bütschi, Florence, Perrone, Maria Dolores, Petit, Florence, Renieri, Alessandra, Romana, Serge, Topa, Alexandra, Vermeesch, Joris Robert, Lenaerts, Tom, Casimir, Georges, Abramowicz, Marc, Bontempi, Gianluca, Vilain, Catheline, Deconinck, Nicolas, Smits, Guillaume, Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Turin, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo' [Trieste], Service de Génétique Clinique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Queen Elizabeth University Hospital (Glasgow), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli Studi di Siena = University of Siena (UNISI), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sahlgrenska University Hospital [Gothenburg], Université Catholique de Louvain = Catholic University of Louvain (UCL), Universiteit Gent = Ghent University [Belgium] (UGENT), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital universitaire Robert-Debré [Paris], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Unité fonctionnelle de génétique clinique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Antwerp (UA), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre for Human Genetics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospitals Leuven [Leuven], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Clermont-Ferrand, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de génétique médicale, CHU Amiens-Picardie, Service Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de Génétique Humaine, Université de Liège-CHU Liège, Service de pédiatre-Néonatologie, CH Villefranche s/Saone, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Medical Genetics, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service d'imagerie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Département de génétique, Allergy Unit - Department of Dermatology, University of Zürich [Zürich] (UZH), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Biology [Utah], University of Utah, Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de biochimie [CHU Caen], Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Département Génétique Médicale-Maternité, Université de Lorraine (UL), Center for Medical Genetics, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Department of Human Genetics, Radboud University Medical Center [Nijmegen], AI-lab, Vakgroep Computerwetenschappen, Universiteit Gent [Ghent], gerard, marion, Università degli studi di Torino = University of Turin (UNITO), Universiteit Gent = Ghent University (UGENT), and Informatics and Applied Informatics
Subjects: Male, 0301 basic medicine, Guanylate Kinases/genetics, Developmental Disabilities, Intellectual disability, lcsh:Medicine, ASPM, brain imaging, brain development, Tumor Suppressor Proteins -- genetics, Genome, Mice, Intellectual Disability -- genetics -- metabolism, Global developmental delay, Copy-number variation, Promoter Regions, Genetic, Child, Genetics (clinical), Epigenomics, Genetics, ATP6 deletion, Membrane Proteins -- genetics, primary microcephaly, Neurodevelopmental disorders, food and beverages, Functional genomics, Exons, DLG2, Promoters, Animals, Female, Guanylate Kinases, Humans, Intellectual Disability, Membrane Proteins, Tumor Suppressor Proteins, Molecular Medicine, Molecular Biology, Sciences bio-médicales et agricoles, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Guanylate Kinases -- genetics, lcsh:QH426-470, Developmental Disabilities/genetics, Developmental Disabilities/metabolism, Intellectual Disability/genetics, Intellectual Disability/metabolism, Membrane Proteins/genetics, Tumor Suppressor Proteins/genetics, Genomics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Promoter Regions, 03 medical and health sciences, Genetic, Complex V deficiency, Next generation sequencing, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene, MCPH, Developmental Disabilities -- genetics -- metabolism, Research, lcsh:R, Human genetics, Mitochondrial disease, lcsh:Genetics, 030104 developmental biology, centrosome, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, NARP syndrome
Abstract: Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017
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24. Management and Survival of Elderly and Very Elderly Patients with Endometrial Cancer: An Age-Stratified Study of 1228 Women from the FRANCOGYN Group

Author: Geoffroy Canlorbe, Charles Coutant, Marcos Ballester, Alexandre Bricou, Nina Hudry, Clothilde Poupon, Emile Daraï, Cyrille Huchon, Lobna Ouldamer, Sofiane Bendifallah, Jean Levêque, Vincent Lavoué, Cyril Touboul, Emilie Raimond, Olivier Graesslin, Pierre Collinet, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Intercommunal Créteil, CHI Créteil-CHI Créteil, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Internal medicine, medicine, Humans, Survival rate, Aged, Gynecology, Aged, 80 and over, 030219 obstetrics & reproductive medicine, business.industry, Endometrial cancer, Age Factors, Middle Aged, medicine.disease, Prognosis, Confidence interval, 3. Good health, Cystadenocarcinoma, Serous, Endometrial Neoplasms, Radiation therapy, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Cohort, Adenocarcinoma, Lymph Node Excision, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Surgery, Female, Neoplasm Recurrence, Local, business, Cohort study, Adenocarcinoma, Clear Cell, Follow-Up Studies
Abstract: International audience; Background - Little data exist about the clinical management and survival of elderly patients with endometrial cancer. This study aimed to evaluate the management of elderly and very elderly patients with endometrial cancer as well as the overall survival (OS) rate, disease-free survival (DFS) rate, and cancer-specific survival (CSS) rate in a multicenter cohort. Methods - Data from 1228 patients with endometrial cancer who received primary treatment between January 2001 and December 2012 were collected from a multicenter database. Clinical management, DFS, CSS, and OS were analyzed. Results - Based on the international endometrial cancer risk classification, 36% (212/582) of women age 65 years or younger, 42% (220/526) of women ages 65-80 years, and 48% (58/120) of women older than 80 years showed high-risk endometrial cancer (p
Published: 2016
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25. Updated French guidelines for diagnosis and management of pelvic ă inflammatory disease

Author: Brun, Jean-Luc, Graesslin, Olivier, Fauconnier, Arnaud, Verdon, Renaud, Agostini, Aubert, Bourret, Antoine, Derniaux, Emilie, Garbin, Olivier, Huchon, Cyrille, Lamy, Catherine, Quentin, Roland, Judlin, Philippe, Gynecologues, Coll Natl, department of pathology, university hospital, parakou, Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de Maladies Infectieuses et Tropicales [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de gynécologie et obstétrique [Poissy - Saint-Germain-en-Laye]], CHI Poissy-Saint-Germain, Pôle de Gynécologie-Obstétrique et Reproduction, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Département de Bactériologie et Hygiène, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: Ofloxacin, medicine.medical_specialty, [SHS.PSY]Humanities and Social Sciences/Psychology, Pelvis, 03 medical and health sciences, 0302 clinical medicine, Anti-Infective Agents, Metronidazole, Pelvic inflammatory disease, medicine, Humans, Sampling (medicine), 030212 general & internal medicine, Antibiotic prophylaxis, Abscess, Societies, Medical, Ultrasonography, 030219 obstetrics & reproductive medicine, business.industry, General surgery, Ceftriaxone, Disease Management, Obstetrics and Gynecology, General Medicine, Evidence-based medicine, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, tubo-ovarian abscess, 3. Good health, Surgery, medicine.anatomical_structure, quality, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Practice Guidelines as Topic, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Pelvic Inflammatory Disease, medicine.drug
Abstract: International audience; Background: Pelvic inflammatory disease (PID) is commonly encountered in ă clinical practice. Objectives: To provide up-to-date guidelines on ă management of PID. Search strategy: An initial search of the Cochrane ă database, PubMed, and Embase was performed using keywords related to PID ă to identify reports in any language published between January 1990 and ă January 2012, with an update in May 2015. Selection criteria: All ă identified reports relevant to the areas of focus were included. Data ă collection and analysis: A level of evidence based on the quality of the ă data available was applied for each area of focus and used for the ă guidelines. Main results: PID must be suspected when spontaneous pelvic ă pain is associated with induced adnexal or uterine pain (grade C). ă Pelvic ultrasonography is necessary to exclude tubo-ovarian abscess ă (grade B). Microbiological diagnosis requires vaginal and endocervical ă sampling for molecular and bacteriological analysis (grade B). ă First-line treatment for uncomplicated PID combines ofloxacin and ă metronidazole for 14 days (grade B). Treatment of tubo-ovarian abscess ă is based on drainage if the collection measures more than 3 cm (grade ă B), with combined ceftriaxone, metronidazole, and doxycycline for 14-21 ă days. Conclusions: Current management of PID requires easily ă reproducible investigations and treatment, and thus can be applied ă worldwide. (C) 2016 International Federation of Gynecology and ă Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Published: 2016
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26. Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation

Author: Martine Doco-Fenzy, Sylvie Jaillard, Odile Boute, Christèle Dubourg, Patrick Edery, Bénédicte Duban-Bedu, Véronique David, Joris Andrieux, Catherine Vincent-Delorme, Isabelle Mortemousque, Albert David, Anne Moncla, Mylène Beri, Dominique Martin-Coignard, Caroline Schluth-Bolard, Nicole Philip, Annick Toutain, Séverine Drunat, Emilie Landais, Sylvie Odent, Chantal Missirian, Cédric Le Caignec, Damien Sanlaville, Jean Mosser, Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), UFR de Médecine, Université de Reims Champagne-Ardenne (URCA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de génétique, Centre Hospitalier Le Mans (CH Le Mans), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Laboratoire de Biochimie Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Plate-forme transcriptome, Université de Rennes (UR), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This research was supported by grants from FEDER, DHOS and STIC 2004/EGMAR., Laboratoire de Génétique Moléculaire, Hôpital Pontchaillou, Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Saint Vincent de Paul-GHICL, Service de Génétique Clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-hôpital Sud, De Villemeur, Hervé, and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: MESH: Chromosome Deletion, Developmental Disabilities, Chromosome Disorders, tau Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Base Sequence, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, MESH: Mental Retardation, Intellectual Disability, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetics, medicine, Humans, Copy-number variation, Allele, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genotyping, Genetics (clinical), 030304 developmental biology, MESH: Chromosome Disorders, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, MESH: Humans, Base Sequence, MESH: Muscle Hypotonia, business.industry, Chromosome, General Medicine, Microdeletion syndrome, medicine.disease, 17q21.31 microdeletion syndrome, Hypotonia, MESH: tau Proteins, MESH: France, MESH: Developmental Disabilities, Muscle Hypotonia, France, Chromosome Deletion, medicine.symptom, Abnormality, business, MESH: Chromosomes, Human, Pair 17, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 17
Abstract: International audience; Chromosome 17q21.31 microdeletion was one of the first genomic disorders identified by chromosome microarrays. We report here the clinical and molecular characterization of a new series of 14 French patients with this microdeletion syndrome. The most frequent clinical features were hypotonia, developmental delay and facial dysmorphism, but scaphocephaly, prenatal ischemic infarction and perception deafness were also described. Genotyping of the parents showed that the parent from which the abnormality was inherited carried the H2 inversion polymorphism, confirming that the H2 allele is necessary, but not sufficient to generate the 17q21.31 microdeletion. Previously reported molecular analyses of patients with 17q21.31 microdeletion syndrome defined a 493 kb genomic fragment that was deleted in most patients after taking into account frequent copy number variations in normal controls, but the deleted interval was significantly smaller (205 kb) in one of our patients, encompassing only the MAPT, STH and KIAA1267 genes. As this patient presents the classical phenotype of 17q21.31 syndrome, these data make it possible to define a new minimal critical region of 160.8 kb, strengthening the evidence for involvement of the MAPT gene in this syndrome.
Published: 2011
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27. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study

Author: Sofiane Bendifallah, Emilie Raimond, Géraldine Bleu, Geoffroy Canlorbe, Olivier Graesslin, Delphine Hudry, Marcos Ballester, Charles Coutant, Pierre Collinet, Emile Daraï, Cyril Touboul, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Intercommunal Créteil, CHI Créteil-CHI Créteil, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de Cancérologie [Paris] (IUC), Administateur, HAL Sorbonne Université, Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Disease-Free Survival, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Carcinosarcoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Interquartile range, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Obesity, Aged, Neoplasm Staging, Proportional Hazards Models, 2. Zero hunger, Gynecology, business.industry, Proportional hazards model, Endometrial cancer, Hazard ratio, Carcinoma, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Endometrial Neoplasms, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Lymph Node Excision, Surgery, Female, Radiotherapy, Adjuvant, France, business, Body mass index, Follow-Up Studies
Abstract: International audience; BACKGROUND: Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups.METHODS: Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables.RESULTS: Distribution of the 729 women with EC according to BMI was BMI < 30 (n = 442; 60.6 %), 30 ≤ BMI < 35 (n = 146; 20 %) and BMI ≥ 35 (n = 141; 19.4 %). Nodal staging was less likely to be performed in women with a BMI ≥ 35 (72 %) than for those with a BMI < 30 (90 %) (p < 0.0001). With a median follow-up of 27 months (interquartile range 13-52), the 3-year RFS was 84.5 %. BMI had no impact on RFS in obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group.CONCLUSION: Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.
Published: 2015
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28. Operative hysteroscopy versus vacuum aspiration for incomplete spontaneous abortion (HY-PER): study protocol for a randomized controlled trial

Author: Aubert Agostini, Nicolas Bourdel, Guillaume Legendre, Cherif Akladios, Olivier Graesslin, Cyrille Huchon, Pierre Panel, Estelle Bauville, Souhail Alouini, HervĂŠ Fernandez, Isabelle Matheron, Jean-Philippe Lucot, Martin Koskas, Xavier Fritel, Cyril Raiffort, Arnaud Fauconnier, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'obstétrique, gynécologie et médecine reproductive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie Obstétrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers, Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-Institut Mère Enfant, Service de Gynécologie - Obstétrique [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Abortion, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, Clinical Protocols, Pregnancy loss, law, Pregnancy, Surveys and Questionnaires, Pharmacology (medical), 030212 general & internal medicine, Incomplete, fertility, Vacuum aspiration, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Abortion, Incomplete, 3. Good health, Treatment Outcome, Vacuum Curettage, Hysteroscopy, Products of conception, Research Design, Female, France, RCT, Adult, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Young Adult, medicine, Humans, business.industry, Induced, Abortion, Induced, Retrospective cohort study, medicine.disease, Surgery, Aspirative curettage, Incomplete miscarriage, business
Abstract: Background Incomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion. Methods After providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team. Discussion If our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22 weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion. Trial registration ClinicalTrials.gov Identifier: NCT02201732; registered on 17 July 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0900-1) contains supplementary material, which is available to authorized users.
Published: 2015
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29. Further delineation of the KAT6B molecular and phenotypic spectrum

Author: DDD study, Gannon, Tamsin, Perveen, Rahat, Schlecht, Hélene, Ramsden, Simon, Anderson, Beverley, Kerr, Bronwyn, Day, Ruth, Banka, Siddharth, Suri, Mohnish, Berland, Siren, Gabbett, Michael, Ma, Alan, Lyonnet, Stan, Cormier-Daire, Valerie, Yilmaz, Rüstem, Borck, Guntram, Wieczorek, Dagmar, Anderlid, Britt-Marie, Smithson, Sarah, Vogt, Julie, Moore-Barton, Heather, Simsek-Kiper, Pelin Ozlem, Maystadt, Isabelle, Destrée, Anne, Bucher, Jessica, Angle, Brad, Mohammed, Shehla, Wakeling, Emma, Price, Sue, Singer, Amihood, Sznajer, Yves, Toutain, Annick, Haye, Damien, Newbury-Ecob, Ruth, Fradin, Melanie, McGaughran, Julie, Tuysuz, Beyhan, Tein, Mark, Bouman, Katelijne, Dabir, Tabib, Van den Ende, Jenneke, Luk, Ho Ming, Pilz, Daniela T, Eason, Jacqueline, Davies, Sally, Reardon, Willie, Garavelli, Livia, Zuffardi, Orsetta, Devriendt, Koen, Armstrong, Ruth, Johnson, Diana, Doco-Fenzy, Martine, Bijlsma, Emilia, Unger, Sheila, Veenstra-Knol, Hermine E, Kohlhase, Jürgen, Lo, Ivan FM, Smith, Janine, Clayton-Smith, Jill, Regional Genetic Service, St Mary's Hospital, Manchester, Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Haukeland University Hospital, Royal Brsibane and Womens' Hospital, The University of Queensland, Department of Clinical Genetics, Children’s Hospital at Westmead, Service de génétique médicale, AP-HP Hôpital Necker - Enfants Malades [Paris], Institute of Human Genetics, Universität Ulm, Institut für Humangenetik [Essen], Universitätsklinikum Essen, Karolinska University Hospital, Karolinska University Hospital [Stockholm], University Hospitals Bristol, University of Birmingham [Birmingham], Hacettepe University Children's Hospital, Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Division of Genetics, Birth Defects and Metabolism, Children's hospital of Chicago, Clinical Genetics, Guy's Hospital [London], North West london hospitals NHS Trust, Department of Clinical Genetics, Northampton General Hospital, Northampton, Barzilai Medical Center, Cliniques Universitaires St Luc, Université Catholique de Louvain (UCL), Service de génétique [Tours], Hôpital Bretonneau - CHRU Tours, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique clinique [Rennes], Université de Rennes 1 (UR1) - CHU Pontchaillou [Rennes] - Hôpital Sud, Pediatrics, Istanbul University Cerrahpasa, Birmingham Women’s Hospital, University of Groningen [Groningen], Belfast City Hospital, Centre For Medical Genetics, Clinical Genetic Service, Department of Health, Institute of Medical Genetics, Heath Park, Cardiff, National Centre for Medical Genetics, Our Lady's Children's Hospital, Crumlin OLCHC, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione 'Istituto Neurologico Nazionale C. Mondino', Dipartimento di Medicina Molecolare, University of Pavia, UZ Leuven - campus Gasthuisberg, East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital, Sheffield Children’s Hospital, Service de Génétique, CHU Reims - Hôpital Maison Blanche - IFR 53, Leiden University Medical Center, Service de Génétique humaine, Université de Lausanne (UNIL), Çocuk Sağlığı ve Hastalıkları, University of Bergen (UiB), Westmead Hospital [Sydney], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Ulm - Ulm University [Ulm, Allemagne], Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Sheffield Children's NHS Foundation Trust, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Leiden University Medical Center (LUMC), UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Nottingham University Hospitals NHS Trust (NUH), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Università degli Studi di Pavia = University of Pavia (UNIPV), Universiteit Leiden-Universiteit Leiden, Université de Lausanne = University of Lausanne (UNIL), DDD study, and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, DNA Mutational Analysis, Medizin, Gene Expression, Kidney, Severity of Illness Index, Craniofacial Abnormalities, Missense mutation, Exome, Genetics (clinical), Histone Acetyltransferases, Genetics, OHDO SYNDROME, Patella, Exons, Hypotonia, 3. Good health, Blepharophimosis/diagnosis, Blepharophimosis/genetics, Child, Preschool, Congenital Hypothyroidism/diagnosis, Congenital Hypothyroidism/genetics, Craniofacial Abnormalities/diagnosis, Craniofacial Abnormalities/genetics, Diagnosis, Differential, Facies, Female, Genetic Association Studies, Genotype, Heart Defects, Congenital/diagnosis, Heart Defects, Congenital/genetics, Histone Acetyltransferases/genetics, Humans, Intellectual Disability/diagnosis, Intellectual Disability/genetics, Joint Instability/diagnosis, Joint Instability/genetics, Kidney/abnormalities, Kidney/pathology, Mutation, Patella/abnormalities, Patella/pathology, Phenotype, Psychomotor Disorders/diagnosis, Psychomotor Disorders/genetics, Scrotum/abnormalities, Scrotum/pathology, Urogenital Abnormalities/diagnosis, Urogenital Abnormalities/genetics, Scrotum, Medical genetics, genitopatellar, Say-Barber-Biesecker, medicine.symptom, Psychomotor disorder, Haploinsufficiency, Heart Defects, Congenital, Joint Instability, medicine.medical_specialty, Biology, Blepharophimosis, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, KAT6B, Article, Intellectual Disability, medicine, Congenital Hypothyroidism, CAUSE GENITOPATELLAR SYNDROME, medicine.disease, blepharophimosis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, DE-NOVO MUTATIONS, Urogenital Abnormalities, Genitopatellar syndrome, HISTONE ACETYLTRANSFERASE KAT6B, Psychomotor Disorders, MENTAL-RETARDATION
Abstract: International audience; KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed.
Published: 2015
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30. Are platelet transfusions harmful in acquired thrombotic thrombocytopenic purpura at the acute phase? Experience of the French thrombotic microangiopathies reference center

Author: Ygal, Benhamou, Jean-Luc, Baudel, Alain, Wynckel, Lionel, Galicier, Elie, Azoulay, François, Provôt, Frédéric, Pène, Jean-Paul, Mira, Claire, Presne, Pascale, Poullin, Jean-Michel, Halimi, Etienne, Rivière, Tarik, Kanouni, Amélie, Seguin, Christiane, Mousson, Aude, Servais, Dominique, Bordessoule, Pierre, Perez, Mohamed, Hamidou, Dominique, Chauveau, Agnès, Veyradier, Paul, Coppo, Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Néphrologie, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Outcomerea Organization, Outcomerea, Service de néphrologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Service d'Hémaphérèse - Médecine Interne, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Bordeaux Segalen - Bordeaux 2, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service de Soins Intensifs [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'Hématologie Biologique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), CHU Necker - Enfants Malades [AP-HP], Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Boullé, Christelle
Subjects: Adult, Male, Purpura, Thrombotic Thrombocytopenic, Platelet Transfusion, Middle Aged, Disease-Free Survival, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Survival Rate, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Article CLINIQUE, Humans, Female, France, ComputingMilieux_MISCELLANEOUS, Retrospective Studies
Abstract: International audience
Published: 2015
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31. A pure familial 6q15q21 split duplication associated with obesity and transmitted with partial reduction

Author: Camille Leroy, Pascale Kleinfinger, Dominique Gaillard, Roselyne Garnotel, Marie-Laurence Poli-Merol, Caroline Fiquet, Martine Doco-Fenzy, M. Béri, Philippe Jonveaux, Pierre-François Souchon, Christine Pietrement, Emilie Landais, Stéphanie Brunet, Valérie Koubi, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Plateforme Régionale de Biologie Innovante, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Laboratoire Pasteur Cerba, Institut Pasteur [Paris]-Laboratoire CERBA [Saint Ouen l'Aumône], Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie, Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Reims), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Matrice extracellulaire et régulations cellulaires (MERC), and Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Adolescent, Offspring, [SDV]Life Sciences [q-bio], Genetic counseling, Inheritance Patterns, Genetic Counseling, Trisomy, Biology, Genetic Heterogeneity, Intellectual Disability, Gene duplication, Genetics, medicine, Humans, Family, Obesity, Child, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Comparative Genomic Hybridization, Genetic heterogeneity, Chromosome, Karyotype, Middle Aged, medicine.disease, Chromosome Banding, Pedigree, Meiosis, Mutagenesis, Insertional, Phenotype, Chromosomes, Human, Pair 6, Female, SNP array, Microsatellite Repeats
Abstract: International audience; Familial transmission of chromosome 6 duplications is rare. We report on the first observation of a maternally-inherited pure segmental 6q duplication split into two segments, 6q15q16.3 and 6q16.3q21, and associated with obesity. Obesity has previously been correlated to chromosome 6 q-arm deletion but has not yet been assessed in duplications. The aim of this study was to characterize the structure of these intrachromosomal insertional translocations by classic cytogenetic banding, array-CGH, FISH, M-banding and genotyping using microsatellites and SNP array analysis, in a mother and four offspring. The duplicated 6q segments, 9.75 Mb (dup 1) and 7.05 Mb (dup 2) in size in the mother, were inserted distally into two distinct chromosome 6q regions. They were transmitted to four offspring. A son and a daughter inherited the two unbalanced insertions and displayed, like the mother, an abnormal phenotype with facial dysmorphism, intellectual disability, and morbid obesity. Curiously, two daughters with a normal phenotype inherited only the smaller segment, 6q16.3q21. The abnormal phenotype was associated with the larger proximal 6q15q16.3 duplication. We hypothesize a mechanism for this exceptional phenomenon of recurrent reduction and transmission of the duplication during meiosis in a family. We expect the interpretation of our findings to be useful for genetic counseling and for understanding the mechanisms underlying these large segmental 6q duplications and their evolution.
Published: 2014
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32. Electron Tomography of Metaphase Nucleolar Organizer Regions: Evidence for a Twisted-Loop Organization

Author: Laurent Héliot, Laurent Lucas, Marc Thiry, Hervé Kaplan, A. Beorchia, M. Menager, Dominique Ploton, Christophe Klein, Marie-Françoise O'Donohue, Martine Doco-Fenzy, Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine de Reims, Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), UTAP, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R) [Liège], Université de Liège-C.H.U. Sart Tilman [Liège], inconnu, and Inconnu
Subjects: Microscopy, Electron, Scanning Transmission, Models, Molecular, Chromosomal Proteins, Non-Histone, Protein Conformation, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, DNA, Ribosomal, KB Cells, Article, law.invention, Mice, 03 medical and health sciences, Confocal microscopy, law, Centromere, Image Processing, Computer-Assisted, Nucleolus Organizer Region, Tumor Cells, Cultured, Animals, Humans, Carcinoma, Ehrlich Tumor, Molecular Biology, Metaphase, 030304 developmental biology, 0303 health sciences, Microscopy, Confocal, 030302 biochemistry & molecular biology, Chromosome, Cell Biology, Chromatin, Cell biology, Electron tomography, Nucleic Acid Conformation, Chromatid, Leukemia, Erythroblastic, Acute, Nucleolus organizer region
Abstract: International audience; Metaphase nucleolar organizer regions (NORs), one of four types of chromosome bands, are located on human acrocentric chromosomes. They contain r-chromatin, i.e., ribosomal genes complexed with proteins such as upstream binding factor and RNA polymerase I, which are argyrophilic NOR proteins. Immunocytochemical and cytochemical labelings of these proteins were used to reveal r-chromatin in situ and to investigate its spatial organization within NORs by confocal microscopy and by electron tomography. For each labeling, confocal microscopy revealed small and large double-spotted NORs and crescent-shaped NORs. Their internal three-dimensional (3D) organization was studied by using electron tomography on specifically silver-stained NORs. The 3D reconstructions allow us to conclude that the argyrophilic NOR proteins are grouped as a fiber of 60-80 nm in diameter that constitutes either one part of a turn or two or three turns of a helix within small and large double-spotted NORs, respectively. Within crescent-shaped NORs, virtual slices reveal that the fiber constitutes several longitudinally twisted loops, grouped as two helical 250- to 300-nm coils, each centered on a nonargyrophilic axis of condensed chromatin. We propose a model of the 3D organization of r-chromatin within elongated NORs, in which loops are twisted and bent to constitute one basic chromatid coil.
Published: 1997
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33. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

Author: Bruno Leheup, Manon Girard, Caroline Rooryck, Elodie Sanchez, David Geneviève, Anouck Schneider, Marie-Ange Delrue, Azzedine Aboura, Magali Tournaire, Laurence Perrin-Sabourin, Emilie Landais, Michel Goossens, Florence Petit, Pierre Sarda, Camille Leroy, Dominique Gaillard, Philippe Jonveaux, Dorothée Cailley, Jacques Puechberty, Joris Andrieux, Laurence Taine, Agnès Ameil, Martine Doco-Fenzy, Geneviève Lefort, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Service de Génétique Médicale du CHU de Bordeaux, Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme TRANSCRIPTOME, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), American Memorial Hospital (Reims), Laboratoire de génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri-Mondor-Albert Chenevier, Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Service de Génétique Clinique Pédiatrique [CHRU Nancy]
Subjects: Male, Genotype, Sequence analysis, [SDV]Life Sciences [q-bio], Nerve Tissue Proteins, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, Genetics, medicine, Humans, Obesity, Child, Gene, In Situ Hybridization, Fluorescence, Genetics (clinical), Sequence Deletion, 030304 developmental biology, Comparative Genomic Hybridization, 0303 health sciences, medicine.diagnostic_test, Genetic heterogeneity, Membrane Proteins, Sequence Analysis, DNA, Phenotype, Molecular biology, Child, Preschool, Chromosomes, Human, Pair 2, Female, Protein Tyrosine Phosphatases, Prader-Willi Syndrome, 030217 neurology & neurosurgery, Genome-Wide Association Study, Transcription Factors, SNP array, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract: International audience; Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.
Published: 2013
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34. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

Author: Stephen W. Scherer, Mònica Gratacòs, Kari Stefansson, Muriel Holder, Unnur Thorsteinsdottir, Lukas Forer, Katharina M. Roetzer, Josette Lucas, Claudia Schurmann, Satu Kaksonen, Armand Valsesia, Carina Wallgren-Pettersson, Barbara Leube, Alexandra I. F. Blakemore, Alexandre Moerman, Marco Belfiore, Anne Faudet, Dominique Gaillard, Roberto Ravazzolo, Dominique Bonneau, Marjo-Riitta Järvelin, Yongguo Yu, Louis Vallée, Bénédicte Demeer, Sophie Visvikis-Siest, Frédérique Béna, Brigitte H. W. Faas, Benoit Arveiler, Georg Homuth, Charles Coutton, Bénédicte de Fréminville, Giorgio Gimelli, Xavier Estivill, Richard I. Fisher, Stefania Gimelli, Wendy Roberts, Jacques S. Beckmann, Emilie Landais, Orah S. Platt, Robin G. Walters, Gudmar Thorleifsson, Alexandre Reymond, Anna-Liisa Hartikainen, Solenn Legallic, James F. Gusella, Peter Vollenweider, Gian Paolo Ramelli, Tõnu Esko, Boris Keren, Nine V A M Knoers, Fanny Morice-Picard, Dominique Campion, Odile Boute, Evica Rajcan-Separovic, Rolph Pfundt, Nathalie Bednarek, Martine Doco-Fenzy, Suzanne M E Lewis, Gérard Didelot, Mylène Beri, Engilbert Sigurdsson, Véronique Satre, Audrey Labalme, Carola Tengstrom, Florian Kronenberg, Florence Petit, Simon Zwolinksi, Philippe Froguel, Paul Elliott, Dorothée Cailley, Christian R. Marshall, Bruno Leheup, Klaus Dieterich, Janina S. Ried, Sylvie Jaillard, Armand Bottani, Stylianos E. Antonarakis, Elisabetta Lapi, Jean-Christophe Cuvellier, Robert M. Witwicki, Gérard Waeber, Christèle Dubourg, Marion Gérard, Lachlan J. M. Coin, Magalie Barth, Anita Kloss-Brandstätter, Vincent Mooser, Cristóbal Richart, Giuseppe Merla, Bénédicte Duban-Bedu, Yiping Shen, Ants Kurg, Audrey Guilmatre, Juliane Hoyer, Susana Jiménez-Murcia, Mafalda Mucciolo, Bai-Lin Wu, Alessandra Ferrarini, Séverine Drunat, Yves Alembik, Páll Magnússon, Han G. Brunner, Maria Antonietta Mencarelli, Dominique Descamps, R. Frank Kooy, Azzedine Aboura, Valérie Layet, Sven Bergmann, Thomas Meitinger, Peter M. Kroisel, Nathalie Van der Aa, Olivier Guillin, Michèle Mathieu-Dramard, Zoltán Kutalik, Elisabeth Flori, Laurent Pasquier, André Reis, Noam D. Beckmann, Bertrand Isidor, Delphine Héron, Philippe Jonveaux, Sergi Villatoro Gomez, Ann Nordgren, José Manuel Fernández-Real, Florence Fellmann, Fernando Fernández-Aranda, Laurence Faivre, Dimitri J. Stavropoulos, Katrin Männik, Christian Gieger, Evald Saemundsen, Agnès Guichet, Jean-Marie Cuisset, R. Touraine, Laura Bernardini, Marie-Ange Delrue, Alessandra Renieri, Omar Gustafsson, Flore Zufferey, David A. Koolen, Massimiliano Rossi, Jacqueline Chrast, Ghislaine Plessis, Faida Walha, Joris Andrieux, Ellen van Binsbergen, Albert David, Catherine Vincent-Delorme, Cédric Le Caignec, Jean Chiesa, Ndeye Coumba Ndiaye, Geraldine Joly Helas, Damien Sanlaville, Anita Rauch, Louise Harewood, Mark I. McCarthy, Bridget A. Fernandez, Sébastien Jacquemont, Hreinn Stefansson, Anneke T. Vulto-van Silfhout, Zdenek Jaros, Matthias Nauck, Hans J. Grabe, Sonia Bouquillon, Mieke M. van Haelst, Andres Metspalu, Loyse Hippolyte, Patrick Callier, Bert B.A. de Vries, Francisco J. Tinahones, Nicole de Leeuw, Julia S. El-Sayed Moustafa, Claudine Rieubland, Kay D. MacDermot, Vittoria Disciglio, Henry Völzke, Caroline Rooryck, Bettina Blaumeiser, Danielle Martinet, Marie-Claude Addor, Bruno Delobel, Jacquemont, S, Reymond, A, Zufferey, F, Harewood, L, Walters, Rg, Kutalik, Z, Martinet, D, Shen, Y, Valsesia, A, Beckmann, Nd, Thorleifsson, G, Belfiore, M, Bouquillon, S, Campion, D, de Leeuw, N, de Vries, Bb, Esko, T, Fernandez, Ba, Fernández-Aranda, F, Fernández-Real, Jm, Gratacòs, M, Guilmatre, A, Hoyer, J, Jarvelin, Mr, Kooy, Rf, Kurg, A, Le Caignec, C, Männik, K, Platt, O, Sanlaville, D, Van Haelst, Mm, Villatoro Gomez, S, Walha, F, Wu, Bl, Yu, Y, Aboura, A, Addor, Mc, Alembik, Y, Antonarakis, Se, Arveiler, B, Barth, M, Bednarek, N, Béna, F, Bergmann, S, Beri, M, Bernardini, L, Blaumeiser, B, Bonneau, D, Bottani, A, Boute, O, Brunner, Hg, Cailley, D, Callier, P, Chiesa, J, Chrast, J, Coin, L, Coutton, C, Cuisset, Jm, Cuvellier, Jc, David, A, de Freminville, B, Delobel, B, Delrue, Ma, Demeer, B, Descamps, D, Didelot, G, Dieterich, K, Disciglio, V, Doco-Fenzy, M, Drunat, S, Duban-Bedu, B, Dubourg, C, El-Sayed Moustafa, J, Elliott, P, Faas, Bh, Faivre, L, Faudet, A, Fellmann, F, Ferrarini, A, Fisher, R, Flori, E, Forer, L, Gaillard, D, Gerard, M, Gieger, C, Gimelli, S, Gimelli, G, Grabe, Hj, Guichet, A, Guillin, O, Hartikainen, Al, Heron, D, Hippolyte, L, Holder, M, Homuth, G, Isidor, B, Jaillard, S, Jaros, Z, Jiménez-Murcia, S, Helas, Gj, Jonveaux, P, Kaksonen, S, Keren, B, Kloss-Brandstätter, A, Knoers, Nv, Koolen, Da, Kroisel, Pm, Kronenberg, F, Labalme, A, Landais, E, Lapi, E, Layet, V, Legallic, S, Leheup, B, Leube, B, Lewis, S, Lucas, J, Macdermot, Kd, Magnusson, P, Marshall, C, Mathieu-Dramard, M, Mccarthy, Mi, Meitinger, T, Mencarelli, Ma, Merla, G, Moerman, A, Mooser, V, Morice-Picard, F, Mucciolo, M, Nauck, M, Ndiaye, Nc, Nordgren, A, Pasquier, L, Petit, F, Pfundt, R, Plessis, G, Rajcan-Separovic, E, Ramelli, Gp, Rauch, A, Ravazzolo, R, Reis, A, Renieri, A, Richart, C, Ried, J, Rieubland, C, Roberts, W, Roetzer, Km, Rooryck, C, Rossi, M, Saemundsen, E, Satre, V, Schurmann, C, Sigurdsson, E, Stavropoulos, Dj, Stefansson, H, Tengström, C, Thorsteinsdóttir, U, Tinahones, Fj, Touraine, R, Vallée, L, van Binsbergen, E, Van der Aa, N, Vincent-Delorme, C, Visvikis-Siest, S, Vollenweider, P, Völzke, H, Vulto-van Silfhout, At, Waeber, G, Wallgren-Pettersson, C, Witwicki, Rm, Zwolinksi, S, Andrieux, J, Estivill, X, Gusella, Jf, Gustafsson, O, Metspalu, A, Scherer, Sw, Stefansson, K, Blakemore, Ai, Beckmann, J, Froguel, P, Faculteit Medische Wetenschappen/UMCG, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Department of Genomics of Common Disease, Imperial College London, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Laboratory Medicine, Boston Children's Hospital, Center for Human Genetic Research, Massachusetts General Hospital [Boston], Ludwig Institute for Cancer Research, deCODE Genetics, deCODE genetics [Reykjavik], Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Estonian Genome and Medicine, University of Tartu, Department of human genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Institute for Genetic and Metabolic Disorders, Institute of Molecular and Cell Biology, Disciplines of Genetics and Medicine, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona-Biomedical Research Institute 'Dr Josep Trueta'-CIBERobn Fisiopatología de la Obesidad y Nutrición, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of child and adolescent health, University of Oulu-Institute of Health Sciences and Biocenter Oulu-National Institute for Health and Welfare [Helsinki], Antwerp University Hospital [Edegem] (UZA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, University Medical Center [Utrecht], Institutes of Biomedical Science, Fudan University [Shanghai]-Children's Hospital, Shanghai Children's Medical Center, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Génétique médicale, Hôpitaux Universitaires de Genève (HUG), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Reims Champagne-Ardenne (URCA), Department of Molecular Genetics, Weizmann Institute of Science [Rehovot, Israël], Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Service de Génétique clinique, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Cytogénétique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-faculté de médecine-pharmacie, AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de Neuropédiatrie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Amiens-Picardie, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service de Génétique Clinique, Department of Biotechnology, Università degli Studi di Siena = University of Siena (UNISI)-Medical Genetics, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Epidemiology and Public Health, Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Department of Experimental Cardiology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Heart Failure Research Center (HFRC), CHU Pitié-Salpêtrière [AP-HP], Institute of human genetics, International Centre for Life, Division of genetic epidemiology, HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Obstetrics and Gynecology, University of Oulu-Institute of Clinical Medicine, Laboratorio di citogenetica, G. Gaslini Institute, Department of Psychiatry and Psychotherapy, Universität Greifswald - University of Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Abteilung für Kinder und Jugendheilkunde, Landesklinikum Waldviertel Zwettl, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), The Habilitation Unit of Folkhalsan, Medical University Graz, Medical Genetics Unit, Children's Hospital Anna Meyer, Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Institute of Human Genetics and Anthropology, Heinrich-Heine University Hospital Duesseldorf, Child and Family Research Institute-University of British Columbia (UBC), North West Thames Regional Genetics Service, Northwick Park & St Marks Hospital, Child and Adolescent Psychiatry, Landspitali University Hospital, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, The Wellcome Trust Centre for Human Genetics [Oxford], Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Genetics, GlaxoSmithKline R&D, GlaxoSmithKline, Institute of Clinical Chemistry and Laboratory Medicine, Génétique cardiovasculaire (GC), Université Henri Poincaré - Nancy 1 (UHP), Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Pathology, Division of pediatrics, Ospedale San Giovanni, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Department of pediatrics and CEBR, Università degli studi di Genova = University of Genoa (UniGe)-G. Gaslini Institute, Department of Internal Medicine, Universitat Rovira i Virgili-University Hospital Juan XXIII-Instituto Salud Carlos III-Ciber Fisiopatologia Obesidad y Nutricion (CIBEROBN), Division of Human Genetics, Department of Paediatrics, Inselspital-University of Bern, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, State Diagnostic, Counseling Center, University of Iceland [Reykjavik], Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Genetic Services, Rinnekoti Research Foundation, Department of Endocrinology and Nutrition, Instituto Salud Carlos III-Clinic Hospital of Virgen de la Victoria-Ciber Fisiopatologia y Nutricion (CIBEROBN), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Institute for Community Medicine, Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Leenaards Foundation Prize (SJ, DM and AR), the Jérôme Lejeune Foundation (AR), the Telethon Action Suisse Foundation (AR), the Swiss National Science Foundation (AR, JSB, SB and SEA), a SNSF Sinergia grant (SJ, DM, SB, JSB and AR), the European Commission anEUploidy Integrated Project grant 037627 (AR, SB, XE, HGB and SEA), the Ludwig Institute for Cancer Research (AV), the Swiss Institute of Bioinformatics (SB, ZK), an Imperial College Dept of Medicine PhD studentship (JSe-SM), the Comprehensive Biomedical Research Centre, Imperial College Healthcare NHS Trust, and the National Institute for Health Research (PE), the Wellcome Trust and the Medical Research Council (AIFB and PF), the Instituto de Salud Carlos III (ISCIII)-FIS, the German Mental Retardation Network funded through a grant of the German Federal Ministry of Education and Research (NGFNplus 01GS08160) to A Reis and European Union-FEDER (PI081714, PS09/01778), SAF2008-02278 (XE, MG, FFA), the Belgian National Fund for Scientific Research - Flanders (NVA, RFK), the Dutch Organisation for Health Research and Development (ZONMW grant 917-86-319) and Hersenstichting Nederland (BBAdV), grant 81000346 from the Chinese National Natural Science Foundation (YGY), the Simons Foundation Autism Research Initiative, Autism Speaks and NIH grant GM061354 (JFG), and the OENB grant 13059 (AK-B). YS holds a Young Investigator Award from the Children's Tumor Foundation and Catalyst Award from Harvard Medical School, and BLW, a Fudan Scholar Research Award from Fudan University, a grant from Chinese National '973' project on Population and Health (2010CB529601) and a grant from Science and Technology Council of Shanghai (09JC1402400). ERS and SL, recipients of the Michael Smith Foundation for Health Research Scholar award, acknowledge the CIHR MOP 74502 operational grant. EGCUT received support from the EU Centre of Excellence in Genomics and FP7 grants #201413 and #245536, from Estonian Government SF0180142s08, SF0180026s09 and SF0180027s10 (AM, KM, AK). The Helmholtz Zentrum Munich and the State of Bavaria financed KORA, also supported by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823), the German Federal Ministry of Education and Research (BMBF), and the Munich Center of Health Sciences (MC Health, LMUinnovativ). CIBEROBN and CIBERESP are initiatives of ISCIII (Spain). SWS holds the GlaxoSmithKline-Canadian Institutes of Health (CIHR) Chair in Genetics, Genomics at the University of Toronto and the Hospital for Sick Children and is supported by Genome Canada and the McLaughlin Centre. deCODE was funded in part by NIH grant MH071425 (KS), EU grant HEALTH-2007-2.2.1-10-223423 (Project PsychCNV) and EU grant IMI-JU-NewMeds., Centre de génomique intégrative, Université de Lausanne (UNIL), Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics, Memorial University of Newfoundland [St. John's], Friedrich Alexander University [Erlangen-Nürnberg], Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Weizmann Institute of Science, IRCCS Casa Sollievo della Sofferenza Hospital, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Etienne-Hôpital nord, Hôpital Saint Vincent de Paul-GHICL, Centre hospitalier de Béthune, Università degli Studi di Siena (UNISI)-Medical Genetics, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Department of Human Genetics, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Innsbruck Medical University [Austria] (IMU)-HMNC Brain Health-Molecular and Clinical Pharmacology, Czech Academy of Sciences [Prague] (ASCR), University of Oxford [Oxford], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, University of Zürich [Zürich] (UZH), Universita degli studi di Genova -G. Gaslini Institute, University of Toronto-The Hospital for Sick Children, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), De Villemeur, Hervé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland., Other departments, Reymond, Alexandre, Antonarakis, Stylianos, Sloan Bena, Frédérique, Bottani, Armand, Callier, Patrick, Gimelli, Stefania, Merla, Giuseppe, Vollenweider, Peter, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Aging, Transcription, Genetic, Adolescent, Adult, Aged, Body Height, Body Mass Index, Case-Control Studies, Child, Child, Preschool, Chromosomes, Human, Pair 16, Cohort Studies, Comparative Genomic Hybridization, Developmental Disabilities, Energy Metabolism, Europe, Female, Gene Dosage, Gene Duplication, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Head, Heterozygote, Humans, Infant, Infant, Newborn, Mental Disorders, Middle Aged, Mutation, North America, Obesity, Phenotype, RNA, Messenger, Sequence Deletion, Thinness, Young Adult, Physiology, RNA, Messenger/analysis/genetics, Genome-wide association study, HIDDEN-MARKOV MODEL, 0302 clinical medicine, Sequence Deletion/genetics, ddc:576.5, 0303 health sciences, education.field_of_study, Body Height/genetics, Genetic Predisposition to Disease/genetics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, population characteristics, Chromosomes, Human, Pair 16/genetics, Human, Locus (genetics), Gene Duplication/genetics, Article, 03 medical and health sciences, Genetic, education, SNP GENOTYPING DATA, Thinness/genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Pair 16, Case-control study, nutritional and metabolic diseases, social sciences, medicine.disease, DEPENDENT PROBE AMPLIFICATION, Human medicine, Body mass index, 030217 neurology & neurosurgery, Messenger, Obesity/genetics, FAILURE-TO-THRIVE, [SDV.GEN] Life Sciences [q-bio]/Genetics, Head/anatomy & histology, METABOLIC SYNDROME, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Genetics, Multidisciplinary, TIME QUANTITATIVE PCR, Failure to thrive, medicine.symptom, Underweight, Transcription, geographic locations, Mutation/genetics, Population, Biology, Chromosomes, 150 000 MR Techniques in Brain Function, medicine, Preschool, 030304 developmental biology, COPY NUMBER VARIATION, Mental Disorders/genetics, Energy Metabolism/genetics, RELATIVE QUANTIFICATION, Gene Dosage/genetics, Newborn, BODY-MASS INDEX, CIRCULAR BINARY SEGMENTATION, RNA, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], human activities, Developmental Disabilities/genetics
Abstract: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance. Leenaards Foundation Jerome Lejeune Foundation Telethon Action Suisse Foundation Swiss National Science Foundation European Commission 037627 QLG1-CT-2000-01643 Ludwig Institute for Cancer Research Swiss Institute of Bioinformatics Imperial College Department of Medicine Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust National Institute for Health Research Wellcome Trust Medical Research Council Instituto de Salud Carlos III (ISCIII)-FIS German Mental Retardation Network German Federal Ministry of Education and Research NGFNplus 01GS08160 European Union PI081714 PS09/01778 201413 245536 info:eu-repo/grantAgreement/EC/FP7/223423 Belgian National Fund for Scientific Research, Flanders Dutch Organisation for Health Research and Development (ZON-MW) 917-86-319 Hersenstichting Nederland (B.B.A.d.V.) Chinese National Natural Science Foundation 81000346 Simons Foundation Autism Research Initiative Autism Speaks NIH GM061354 MH071425 Oesterreichische Nationalbank (OENB) 13059 Children's Tumor Foundation Harvard Medical School Fudan University Chinese National '973' project on Population and Health 2010CB529601 Science and Technology Council of Shanghai 09JC1402400 Michael Smith Foundation for Health CIHR MOP 74502 Estonian Government SF0180142s08 SF0180026s09 SF0180027s10 Helmholtz Zentrum Munich State of Bavaria German National Genome Research Network 01GS0823 German Federal Ministry of Education and Research (BMBF) Munich Center of Health Sciences (MC Health, LMUinnovativ) Genome Canada McLaughlin Centre Academy of Finland 104781 120315 129269 1114194 University Hospital Oulu Biocenter University of Oulu, Finland 75617 NHLBI 5R01HL087679-02 1RL1MH083268-01 NIH/NIMH 5R01MH63706:02 ENGAGE project Medical Research Council, UK G0500539 G0600705 Academy of Finland Biocentrum Helsinki SAF2008-02278 HEALTH-F4-2007-201413
Published: 2011
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35. Receptor for advanced glycation end-products (RAGE) modulates neutrophil adhesion and migration on glycoxidated extracellular matrix

Author: Ann Marie Schmidt, Elise Lambert, Philippe Gillery, Roselyne Garnotel, J.M. Zahm, Philippe Rieu, J Chanard, Fabien Vitry, Noël Bonnet, Fatouma Touré, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Matrice extracellulaire et régulations cellulaires (MERC), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), Department of Surgery, Columbia University College of Physicians and Surgeons, Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, Zahm, Jean-Marie, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: MAPK/ERK pathway, Glycosylation, Neutrophils, Receptor for Advanced Glycation End Products, Chemokinesis, MESH: Rabbits, MESH: Neutrophils, Biochemistry, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, RAGE (receptor), Collagen receptor, Tendons, Extracellular matrix, Cytosol, 0302 clinical medicine, MESH: Cytosol, Cell Movement, Reference Values, Glycation, MESH: Animals, Receptors, Immunologic, MESH: Cell Movement, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Chemistry, MESH: Peptides, MESH: Reference Values, Life Sciences, MESH: Glycosylation, MESH: Tendons, Extracellular Matrix, 3. Good health, Cell biology, 030220 oncology & carcinogenesis, Rabbits, Ion Channel Gating, Type I collagen, Adult, MESH: Rats, MESH: Extracellular Matrix, Antibodies, MESH: Cell Adhesion, 03 medical and health sciences, Cell Adhesion, Animals, Humans, Molecular Biology, MESH: Receptors, Immunologic, 030304 developmental biology, MESH: Humans, MESH: Antibodies, Chemotaxis, MESH: Adult, Cell Biology, MESH: Ion Channel Gating, Rats, Immunology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Peptides
Abstract: International audience; AGEs (advanced glycation end-products) accumulate in collagen molecules during uraemia and diabetes, two diseases associated with high susceptibility to bacterial infection. Because neutrophils bind to collagen during their locomotion in extravascular tissue towards the infected area we investigated whether glycoxidation of collagen (AGE-collagen) alters neutrophil migration. Type I collagen extracted from rat tail tendons was used for in vitro glycoxidation (AGE-collagen). Neutrophils were obtained from peripheral blood of healthy adult volunteers and were used for the in vitro study of adhesion and migration on AGE- or control collagen. Glycoxidation of collagen increased adhesion of neutrophils to collagen surfaces. Neutrophil adhesion to AGE-collagen was inhibited by a rabbit anti-RAGE (receptor for AGEs) antibody and by PI3K (phosphoinositide 3-kinase) inhibitors. No effect was observed with ERK (extracellular-signal-regulated kinase) or p38 MAPK (mitogen-activated protein kinase) inhibitors. AGE-collagen was able to: (i) induce PI3K activation in neutrophils, and (ii) inhibit chemotaxis and chemokinesis of chemoattractant-stimulated neutrophils. Finally, we found that blocking RAGE with anti-RAGE antibodies or inhibiting PI3K with PI3K inhibitors restored fMLP (N-formylmethionyl-leucyl-phenylalanine)-induced neutrophil migration on AGE-collagen. These results show that RAGE and PI3K modulate adhesion and migration rate of neutrophils on AGE-collagen. Modulation of adhesiveness may account for the change in neutrophil migration rate on AGE-collagen. As neutrophils rely on their ability to move to perform their function as the first line of defence against bacterial invasion, glycoxidation of collagen may participate in the suppression of normal host defence in patients with diabetes and uraemia.
Published: 2008
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36. The clinical spectrum associated with a chromosome 17 short arm proximal duplication (dup 17p11.2) in three patients

Author: Anouck Schneider, Corinne Magdelaine, Maroun Khoury, Bérengère de Martinville, Dominique Gaillard, Odile Goze-Martineau, Louis Vallée, Rabih Klink, Feng Zhang, Martine Doco-Fenzy, Muriel Holder-Espinasse, Eric Bieth, Marie-Claire Vincent, James R. Lupski, Sylvie Manouvrier-Hanu, Joris Andrieux, Jean-Marie Cuisset, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Service de Biochimie et Génétique Moléculaire [CHU Limoges], CHU Limoges, Biomolécules Thérapies anti-tumorales (EA4021), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)
Subjects: Male, Potocki–Lupski syndrome, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biology, Contiguous gene syndrome, 03 medical and health sciences, MESH: Child, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene duplication, Genetics, medicine, MESH: Chromosome Aberrations, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: In Situ Hybridization, Fluorescence, Child, Gene, Genetics (clinical), In Situ Hybridization, Fluorescence, 030304 developmental biology, Chromosome Aberrations, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, MESH: Humans, MESH: Child, Preschool, 030305 genetics & heredity, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH: Male, 3. Good health, Chromosome 17 (human), [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Microsatellite, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Homologous recombination, MESH: Chromosomes, Human, Pair 17, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Comparative genomic hybridization, Chromosomes, Human, Pair 17
Abstract: International audience; The p11.2-p12 region of human chromosome 17 is gene rich and composed of at least two genomically unstable domains: the Smith-Magenis syndrome region (17p11.2) and the Charcot-Marie-Tooth region (17p12), both of which are flanked by several low-copy repeat sequences. Homologous recombination between these flanking repeats results in either deletion- or duplication-associated phenotypes caused by a gene dosage effect. We report on the clinical phenotype of three patients presenting with either a 17p11.2 or 17p11.2p12 duplication, revealed by chromosome analysis and confirmed by fluorescent in situ hybridization analysis, high resolution genomic analysis of the 17p region using oligonucleotide array comparative genomic hybridization, and molecular studies with microsatellite markers. Two patients carry the 17p11.2 duplication, while the third one shows a larger duplication including the 17p12 region. The facial features observed in our patients include triangular face, full cheeks, smooth philtrum, thin upper lip, dental malocclusion, irregular eyebrows, and sparse hair, all of which are consistent with the pure proximal dup 17p phenotype. The patients' other clinical features are compared with previously published cases.
Published: 2008
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37. Compliance of abdominal aortic aneurysms before and after stenting with tissue doppler imaging: evolution during follow-up and correlation with aneurysm diameter

Author: Claude Marcus, Anne Long, Fabien Vitry, Jean Noel Albertini, Laurence Rouet, Claude Clément, Vascular Medicine, Centre Hospitalier Universitaire de Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), MedisysResearch Lab (Medisys), Philips Research, Unité de recherche clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche, and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, MESH: Dilatation, Pathologic, Time Factors, medicine.medical_treatment, MESH: Aorta, Abdominal, 02 engineering and technology, 030204 cardiovascular system & hematology, Endovascular aneurysm repair, Doppler imaging, MESH: Blood Vessel Prosthesis, Aortic aneurysm, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Double-Blind Method, Aorta, Abdominal, Prospective Studies, MESH: Treatment Outcome, MESH: Aged, Aged, 80 and over, MESH: Compliance, MESH: Follow-Up Studies, General Medicine, MESH: Predictive Value of Tests, Abdominal aortic aneurysm, Prosthesis Failure, MESH: Reproducibility of Results, Treatment Outcome, cardiovascular system, Female, Stents, Radiology, MESH: Pressure, Cardiology and Cardiovascular Medicine, MESH: Aortic Aneurysm, Abdominal, Compliance, Dilatation, Pathologic, medicine.medical_specialty, Aortic Rupture, 0206 medical engineering, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, Aneurysm, Double-Blind Method, Blood vessel prosthesis, Predictive Value of Tests, Elastic Modulus, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Pressure, Humans, cardiovascular diseases, Thrombus, Aged, MESH: Humans, business.industry, MESH: Time Factors, MESH: Aortic Rupture, Reproducibility of Results, Ultrasonography, Doppler, MESH: Blood Vessel Prosthesis Implantation, medicine.disease, 020601 biomedical engineering, MESH: Male, MESH: Prospective Studies, Blood Vessel Prosthesis, MESH: Stents, MESH: Ultrasonography, Doppler, MESH: Elastic Modulus, MESH: Prosthesis Failure, Surgery, business, MESH: Female, Abdominal surgery, Aortic Aneurysm, Abdominal, Follow-Up Studies
Abstract: International audience; Usual imaging after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA) consists of AAA diameter monitoring and endoleak detection. Among additional predictor parameters previously proposed to help clinicians in better identifying subgroups of AAA still at risk of rupture, AAA wall motion after EVAR has been studied, but its value was not clearly established. Tissue Doppler imaging (TDI) is an ultrasonographic modality which allows wall motion measurements along an arterial segment. The aim of the current study was to analyze AAA wall motion with TDI before and after EVAR and to describe its evolution in patients with more than 1 month of follow-up. Twenty-five consecutive patients undergoing EVAR between February 2005 and June 2007 gave informed consent to be prospectively investigated with the TDI system before EVAR and at each visit during follow-up. The mean (SD) follow-up was 13.7 (9.7) months. Maximum mean segmental dilation (MMSD), segmental compliance, dilation at maximum diameter, pressure strain elastic modulus (Ep), and stiffness were compared between three periods (before stenting, before discharge, and at last follow-up), and their relation with AAA diameter was analyzed. A significant decrease in AAA compliance was immediately observed after successful EVAR and remained stable during later follow-up. On the other hand, AAA diameter progressively decreased along time and was statistically lower at the last control compared to the initial value. MMSD, segmental compliance, and dilation at maximum diameter were positively related to AAA diameter. This means that the larger the AAA diameter after stenting, the higher the value for these parameters can be expected. On the contrary, percentage of AAA diameter decrease and percentage of MMSD decrease were not related after successful EVAR. There was no parallelism between loss in compliance and diameter decrease along time, and there is not a unique pattern of AAA diameter and compliance evolution after EVAR. Even if comparison between patients without and with endoleak was weak due to the small sample of the latter group (five patients with endoleak), compliance tended to be greater in case of endoleak. AAA wall motion after successful EVAR reflects complex interactions between all the components of the stented aneurysm which evolve over time, including true compliance of the aneurysm wall itself; intra-aneurysm sac pressure with possible different effects for peak, mean, and pulse pressures; remodeling of the thrombus; stiffness characteristics of the graft; and systemic pressure. Combining simultaneous MMSD records with actual intrasaccular pressure measurements in patients with and without endoleak would improve our understanding of the clinical pulsatility mechanism within AAA after EVAR.
Published: 2008
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