19 results on '"Boddaert, Nathalie"'
Search Results
2. Radiation-free and injection-free imaging of the paediatric chest using a magnetic resonance imaging protocol including zero time echo sequence (3D-ZTE)
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Drummond, David, Marquant, Fabienne, Zanelli, Elisa, Lozach, Cécile, Boddaert, Nathalie, Taam, Rola Abou, Neven, Bénédicte, Le Bourgeois, Muriel, Hadchouel, Alice, Sarnacki, Sabine, Elie, Caroline, Delacourt, Christophe, and Berteloot, Laureline
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- 2024
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3. Specific brain MRI features of constitutional mismatch repair deficiency syndrome in children with high-grade gliomas
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Raveneau, Magali, Guerrini-Rousseau, Léa, Levy, Raphael, Roux, Charles-Joris, Bolle, Stéphanie, Doz, François, Bourdeaut, Franck, Colas, Chrystelle, Blauwblomme, Thomas, Beccaria, Kevin, Tauziède-Espariat, Arnault, Varlet, Pascale, Dufour, Christelle, Grill, Jacques, Boddaert, Nathalie, and Dangouloff-Ros, Volodia
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- 2024
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4. Imaging features to distinguish posterior fossa ependymoma subgroups
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Leclerc, Thomas, Levy, Raphael, Tauziède-Espariat, Arnault, Roux, Charles-Joris, Beccaria, Kevin, Blauwblomme, Thomas, Puget, Stéphanie, Grill, Jacques, Dufour, Christelle, Guerrini-Rousseau, Léa, Abbou, Samuel, Bolle, Stéphanie, Roux, Alexandre, Pallud, Johan, Provost, Corentin, Oppenheim, Catherine, Varlet, Pascale, Boddaert, Nathalie, and Dangouloff-Ros, Volodia
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- 2024
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5. The longitudinal evolution of cerebral blood flow in children with tuberous sclerosis assessed by arterial spin labeling magnetic resonance imaging may be related to cognitive performance
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Rutten, Caroline, Fillon, Ludovic, Kuchenbuch, Mathieu, Saitovitch, Ana, Boisgontier, Jennifer, Chemaly, Nicole, Breuillard, Delphine, Ouss, Lisa, Dangouloff-Ros, Volodia, Blauwblomme, Thomas, Zilbovicius, Monica, Nabbout, Rima, and Boddaert, Nathalie
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- 2023
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6. Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features
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Calmon, Raphaël, Dangouloff-Ros, Volodia, Varlet, Pascale, Deroulers, Christophe, Philippe, Cathy, Debily, Marie-Anne, Castel, David, Beccaria, Kevin, Blauwblomme, Thomas, Grevent, David, Levy, Raphael, Roux, Charles-Joris, Purcell, Yvonne, Saitovitch, Ana, Zilbovicius, Monica, Dufour, Christelle, Puget, Stéphanie, Grill, Jacques, and Boddaert, Nathalie
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- 2021
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7. Genotype–phenotype correlations in individuals with pathogenic RERE variants
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Jordan, Valerie K, Fregeau, Brieana, Ge, Xiaoyan, Giordano, Jessica, Wapner, Ronald J, Balci, Tugce B, Carter, Melissa T, Bernat, John A, Moccia, Amanda N, Srivastava, Anshika, Martin, Donna M, Bielas, Stephanie L, Pappas, John, Svoboda, Melissa D, Rio, Marlène, Boddaert, Nathalie, Cantagrel, Vincent, Lewis, Andrea M, Scaglia, Fernando, Network, Undiagnosed Diseases, Kohler, Jennefer N, Bernstein, Jonathan A, Dries, Annika M, Rosenfeld, Jill A, DeFilippo, Colette, Thorson, Willa, Yang, Yaping, Sherr, Elliott H, Bi, Weimin, and Scott, Daryl A
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Congenital Structural Anomalies ,Genetics ,Genetic Testing ,Rare Diseases ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Carrier Proteins ,Child ,Preschool ,Fatal Outcome ,Female ,Genetic Association Studies ,Humans ,Infant ,Male ,Mutation ,Young Adult ,1p36 deletion syndrome ,CHARGE syndrome ,CHD7 ,genotype-phenotype correlations ,NEDBEH ,RERE ,Undiagnosed Diseases Network ,Clinical Sciences ,Genetics & Heredity - Abstract
Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype-phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7.
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- 2018
8. Performance of Non‐EPI DW MRI for Pediatric Cholesteatoma Follow‐Up.
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Daoudi, Hannah, Levy, Raphaël, Baudouin, Robin, Couloigner, Vincent, Leboulanger, Nicolas, Garabédian, Eréa‐Noel, Belhous, Kahina, Boddaert, Nathalie, Denoyelle, Françoise, and Simon, François
- Abstract
Objective: To evaluate the accuracy, sensitivity, and specificity of nonecho planar (non‐EPI) diffusion‐weighted (DW) magnetic resonance imaging (MRI) to detect residual cholesteatoma in children. Study Design: Retrospective study. Setting: Tertiary comprehensive hospital. Methods: Children operated on for a first‐stage cholesteatoma procedure from 2010 to 2019 were included. MRIs were performed with non‐EPI DW sequences. Initial reports were collected, indicating the presence or absence of hyperintensity suggestive of cholesteatoma. Three hundred twenty‐three MRIs were correlated with the subsequent surgery (66%) or year‐later MRI (21%), or were considered accurate if performed 5 years or more after the last surgery (13%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging procedure for the detection of cholesteatoma were calculated. Results: Two hundred twenty‐four children with mean age of 9 ± 4 years old presented with cholesteatoma. MRIs were performed 27 ± 24 months after surgery. Residual cholesteatoma was diagnosed in 35%. The sensitivity, specificity, PPV, and NPV of MRI were 62%, 86%, 74%, and 78%, respectively. Accuracy, sensitivity, and specificity increased significantly over time (multivariate analysis). The mean delay after last surgery was of 30 ± 2.0 months for accurate MRI (true positive or negative) versus 17 ± 2.0 months for nonaccurate (false positive or negative) MRIs (p <.001). Conclusion: However, long the delay after the last surgery, the sensitivity of non‐EPI diffusion sequence MRI in children has limitations for the detection of residual cholesteatoma. Surveillance for residual cholesteatoma should incorporate findings at primary surgery, surgeon experience, a low threshold for second‐look procedures, and routine imaging. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Craniopharyngioma: the pendulum of surgical management
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Sainte-Rose, Christian, Puget, Stéphanie, Wray, Alison, Zerah, Michel, Grill, Jacques, Brauner, Raja, Boddaert, Nathalie, and Pierre-Kahn, Alain
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- 2005
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10. Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome
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Arrondel, Christelle, Missoury, Sophia, Snoek, Rozemarijn, Patat, Julie, Menara, Giulia, Collinet, Bruno, Liger, Dominique, Durand, Dominique, Gribouval, Olivier, Boyer, Olivia, Buscara, Laurine, Martin, Gaëlle, Machuca, Eduardo, Nevo, Fabien, Lescop, Ewen, Braun, Daniela A., Boschat, Anne-Claire, Sanquer, Sylvia, Guerrera, Ida Chiara, Revy, Patrick, Parisot, Mélanie, Masson, Cécile, Boddaert, Nathalie, Charbit, Marina, Decramer, Stéphane, Novo, Robert, Macher, Marie-Alice, Ranchin, Bruno, Bacchetta, Justine, Laurent, Audrey, Collardeau-Frachon, Sophie, van Eerde, Albertien M., Hildebrandt, Friedhelm, Magen, Daniella, Antignac, Corinne, van Tilbeurgh, Herman, Mollet, Géraldine, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Molecular bases of hereditary kidney diseases: nephronophthisis and hypodysplasia (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Molecular medicine [Utrecht], University Medical Center [Utrecht], Department of Genetics [Utrecht, the Netherlands], Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie pédiatrique [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), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Department of Medicine [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Boston Children's Hospital, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie métabolique [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), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Genome dynamics in the immune system (Equipe Inserm U1163), Plateforme de génomique [SFR Necker], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Service de Pédiatrie - Néphrologie, Médecine interne, Hypertension, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Unité Néphrologie Pédiatrique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Service de Pathologie [Hôpital Femme-Mère-Enfant, HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Division of Nephrology [Boston, MA, USA] (Department of Medicine), Boston Children's Hospital, Pediatric Nephrology Institute [Haifa, Israel], Rambam Health Care Campus [Haifa, Israel]-Technion Faculty of Medicine [Haifa, Israel], Service de Génétique Médicale [CHU Necker], This work was supported by the Fondation pour le Recherche Médicale (project DEQ2015031682) (to C. Antignac), the European Union’s Seventh Framework Programme (FP7/2012, grant 305608 EURenOmics) (to C. Antignac), the Investments for the Future Program (grant ANR-10-IAHY-01) (to C. Antignac), ANR KeoGamo (ANR-18-CE11-0008-01) (to G. Mollet and H.v.T.). This work was supported by the French Infrastructure for Integrated Structural Biology (FRISBI) (ANR-10-INSB-05–01) (to H.v.T.) and the Dutch Kidney Foundation (grant 15OP14) (to A.M.v.E.). S.M. is supported by a Ph.D. grant of the Fondation pour le Recherche Médicale (FRM). P.R. is a scientist from Centre National de la Recherche Scientifique (CNRS)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-CE11-0008,KeoGamo,Caractérisation fonctionnelle du complexe KEOPS et son implication dans le syndrome de Galloway-Mowat(2018), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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)-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)-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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Gribouval, Olivier, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Caractérisation fonctionnelle du complexe KEOPS et son implication dans le syndrome de Galloway-Mowat - - KeoGamo2018 - ANR-18-CE11-0008 - AAPG2018 - VALID, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, and European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID
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Male ,Adenosine ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Nephrosis/genetics ,Microcephaly/genetics ,RNA, Transfer ,MESH: Child ,lcsh:Science ,Child ,MESH: Intrinsically Disordered Proteins ,Research Support, Non-U.S. Gov't ,Medical genetics ,Nuclear Proteins ,RNA-Binding Proteins ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,MESH: Nephrosis ,Microcephaly ,Nephrosis ,Intrinsically Disordered Proteins/genetics ,Female ,Multiprotein Complexes/chemistry ,RNA, Transfer/genetics ,RNA-Binding Proteins/chemistry ,MESH: Mutation ,MESH: GTP-Binding Proteins ,Science ,Nuclear Proteins/chemistry ,MESH: Microcephaly ,Article ,MESH: Hernia, Hiatal ,GTP-Binding Proteins ,Hernia, Hiatal/genetics ,GTP-Binding Proteins/chemistry ,Journal Article ,Humans ,X-ray crystallography ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,MESH: Multiprotein Complexes ,MESH: Adenosine ,MESH: RNA, Transfer ,RNA modification ,MESH: Male ,tRNAs ,Intrinsically Disordered Proteins ,MESH: RNA-Binding Proteins ,Hernia, Hiatal ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Multiprotein Complexes ,Mutation ,lcsh:Q ,Adenosine/analogs & derivatives ,MESH: Nuclear Proteins ,MESH: Female - Abstract
N6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex., The biosynthesis of N6-threonylcarbamoylated adenosine 37 in tRNA (t6A) involves the YRDC enzyme and the KEOPS complex. Here, the authors report mutations in YRDC and the KEOPS component GON7 in Galloway-Mowat syndrome and determine the crystal structure of a GON7-containg subcomplex that suggests a role in KEOPS complex stability.
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- 2019
11. Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma
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Pagès, Mélanie, Beccaria, Kevin, Boddaert, Nathalie, El Saffroy, Raphael, Besnard, Aurore, Castel, David, Fina, Frederic, Barets, Doriane, Barret, Emilie, Lacroix, Ludovic, Bielle, Franck, Andreiuolo, Felipe, Tauziède-Espariat, Arnault, Figarella-Branger, Dominique, Puget, Stéphanie, Grill, Jacques, Chretien, Fabrice, Varlet, Pascale, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Département de biochimie, Ecole Polytechnique Féminine ((EPF)), Ecole d'Ingénieurs, Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de biologie et pathologie médicales [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Service de Neuropathologie [CHU Pitié Salpêtrière], 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 Pasteur [Paris], Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Ecole Polytechnique Féminine ( (EPF) ), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] ( UMR 8203 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital Nord [CHU - APHM], Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] ( ACPNP ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service de neuropathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), figarella-branger, dominique, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Male ,Proto-Oncogene Proteins B-raf ,Adolescent ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Histones ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,H3 K27M ,Humans ,Spinal Cord Neoplasms ,[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics ,Child ,neoplasms ,Research Articles ,ganglioglioma ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Brain Neoplasms ,BRAF V600E ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,midline ,Immunohistochemistry ,Treatment Outcome ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Child, Preschool ,Mutation ,Female ,Neoplasm Grading ,Follow-Up Studies - Abstract
International audience; Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As co-occurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. Twenty-seven patients (50%) possessed the BRAF V600E mutation. The frequency of the co-occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M mutation was detected in the absence of the BRAF V600E mutation. Double-immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were present in both the glial and neuronal components. Immunopositivity for the BRAF V600E mutant protein correlated with BRAF mutation status as detected by massARRAY or digital droplet PCR. The median follow-up of patients with double mutation was 4 years. One patient died of progressive disease 8 years after diagnosis, whereas the four other patients were all alive with stable disease at the last clinical follow-up (at 9 months, 1 year and 7 years) without adjuvant therapy. We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.
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- 2018
12. Common genetic variants influence human subcortical brain structures
- Author
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Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), The Hospital for sick children [Toronto] (SickKids), Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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)-Université Paris-Saclay-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)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), 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)-Université Paris-Saclay, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US
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CHROMATIN ,Male ,Netherlands Twin Register (NTR) ,Aging ,Identification ,nervous-system ,human geography ,SEGMENTATION ,Caudate nucleus ,Apoptosis ,Expression ,Genome-wide association study ,Striatum ,Hippocampal formation ,Hippocampus ,BASAL GANGLIA ,130 000 Cognitive Neurology & Memory ,Basal ganglia ,genetics [Gene Expression Regulation, Developmental] ,Hippocampal ,Child ,anatomy & histology [Skull] ,Aged, 80 and over ,Genetics ,Sex Characteristics ,KINECTIN ,Genome-wide association ,Multidisciplinary ,Putamen ,Brain ,Gene Expression Regulation, Developmental ,blood ,brain ,disease incidence ,genetic variation ,neurology ,Organ Size ,Human brain ,Middle Aged ,organization ,Magnetic Resonance Imaging ,genetics [Genetic Variation] ,Chromatin ,Dynamics ,genetics [Membrane Proteins] ,medicine.anatomical_structure ,genetics [Aging] ,Anatomy & histology ,[ SCCO.NEUR ] Cognitive science/Neuroscience ,Female ,ddc:500 ,anatomy & histology [Caudate Nucleus] ,Neuroinformatics ,EXPRESSION ,Adult ,Adolescent ,Evolution ,anatomy & histology [Hippocampus] ,ORGANIZATION ,genetics [Genetic Loci] ,Biology ,Article ,Young Adult ,SDG 3 - Good Health and Well-being ,Journal Article ,medicine ,Humans ,GENOME-WIDE ASSOCIATION ,General ,genetics [Apoptosis] ,Kinectin ,Aged ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,HIPPOCAMPAL ,IDENTIFICATION ,genetics [Organ Size] ,[SCCO.NEUR]Cognitive science/Neuroscience ,Skull ,segmentation ,Genetic Variation ,Membrane Proteins ,NERVOUS-SYSTEM ,anatomy & histology [Putamen] ,Genetic Loci ,KTN1 protein, human ,Caudate Nucleus ,anatomy & histology [Brain] ,Neuroscience ,Genome-Wide Association Study - Abstract
Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.
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- 2015
13. LIS1-Related Isolated Lissencephaly: Spectrum of Mutations and Relationships With Malformation Severity
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Saillour, Yoann, Carion, Nathalie, Quelin, Chloe, Leger, Pierre-Louis, Boddaert, Nathalie, Elie, Caroline, Toutain, Annick, Mercier, Sandra, Barthez, Marie Anne, Milh, Mathieu, Joriot, Sylvie, Des Portes, Vincent, Philip, Nicole, Broglin, Dominique, ROUBERTIE, Agathe, Pitelet, Gaëlle, Moutard, Marie Laure, Pinard, Jean-Marc, Cancès, Clément, Cances, Claude, Kaminska, Anna, Chelly, Jamel, Beldjord, Chérif, Bahi-Buisson, Nadia, 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), Laboratoire de biochimie et génétique moléculaire, 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), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-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), 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 d'informatique médicale et biostatistiques [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 génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, 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 pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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 Neuro-pédiatrie[Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neuropédiatrie, Université de Lyon-CHU de Lyon, 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 neuropédiatrie, CHU Hôpital, Hôpital l'Archet, Unité de Neurologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Département de Pédiatrie, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département de Pédiatrie, CHU Toulouse [Toulouse], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), This study was supported by the French National Programme Hospitalier de Recherche Clinique (2003-32) and the Société d'Etudes et de Soins pour les Enfants Paralysés et Polymalformés., Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 ), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Service de Réanimation Néonatale et Pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Maladies Rares ' malformations et maladies congénitales du cervelet ', Hospices Civils de Lyon (HCL)-CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches]-Département de Pédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Diderot - Paris 7 ( UPD7 ) -IFR2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Bretonneau-CHRU Tours, 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 ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), 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 ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ) -CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches]-Département de Pédiatrie, Laboratoire Jacques-Louis Lions ( LJLL ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Genotype ,DNA Mutational Analysis ,Lissencephaly ,Classical Lissencephalies and Subcortical Band Heterotopias ,MESH : 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics* Adolescent Adult Brain/pathology* Child Child, Preschool Classical Lissencephalies and Subcortical Band Heterotopias/classification Classical Lissencephalies and Subcortical Band Heterotopias/diagnosis Classical Lissencephalies and Subcortical Band Heterotopias/genetics* DNA Mutational Analysis* Female Genotype* Humans Infant Magnetic Resonance Imaging* Male Microtubule-Associated Proteins/genetics* Neurologic Examination* Phenotype Young Adult ,medicine.disease_cause ,Central nervous system disease ,03 medical and health sciences ,PAFAH1B1 ,Young Adult ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,medicine ,Medication Resistant Epilepsy ,Humans ,Child ,030304 developmental biology ,Neurologic Examination ,0303 health sciences ,Mutation ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Brain ,Infant ,medicine.disease ,Phenotype ,Magnetic Resonance Imaging ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Child, Preschool ,1-Alkyl-2-acetylglycerophosphocholine Esterase ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,[ SCCO ] Cognitive science ,business ,Microtubule-Associated Proteins ,030217 neurology & neurosurgery - Abstract
International audience; Objective: With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype.Design: Retrospective study.Subjects: A total of 63 patients with posteriorly predominant lissencephaly.Interventions: Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined.Results: Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly.Conclusion: Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.
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- 2009
14. Characteristics of defenestrating craniofacial injuries in pediatric patients.
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Joly, Aline, Pineau, Virginie, Montmayeur, Juliette, Meyer, Philippe, Belhous, Kahina, Boddaert, Nathalie, Picard, Arnaud, and Kadlub, Natacha
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- 2017
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15. From splitting GLUT1 deficiency syndromes to overlapping phenotypes.
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Hully, Marie, Vuillaumier-Barrot, Sandrine, Le Bizec, Christiane, Boddaert, Nathalie, Kaminska, Anna, Lascelles, Karine, de Lonlay, Pascale, Cances, Claude, des Portes, Vincent, Roubertie, Agathe, Doummar, Diane, LeBihannic, Anne, Degos, Bertrand, de Saint Martin, Anne, Flori, Elisabeth, Pedespan, Jean Michel, Goldenberg, Alice, Vanhulle, Catherine, Bekri, Soumeya, and Roubergue, Anne
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GLUCOSE transporter 1 deficiency syndrome , *GENETIC disorders , *PHENOTYPES , *GENETIC mutation , *GLUCOSE in the body , *GENETICS of epilepsy - Abstract
Introduction Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder due to mutations or deletions in SLC2A1 , resulting in impaired glucose uptake through the blood brain barrier. The classic phenotype includes pharmacoresistant epilepsy, intellectual deficiency, microcephaly and complex movement disorders, with hypoglycorrhachia, but milder phenotypes have been described (carbohydrate-responsive phenotype, dystonia and ataxia without epilepsy, paroxysmal exertion-induced dystonia). The aim of our study was to provide a comprehensive overview of GLUT1DS in a French cohort. Methods 265 patients were referred to the French national laboratory for molecular screening between July 2006 and January 2012. Mutations in SLC2A1 were detected in 58 patients, with detailed clinical data available in 24, including clinical features with a focus on their epileptic pattern and electroencephalographic findings, biochemical findings and neuroimaging findings. Results 53 point mutations and 5 deletions in SLC2A1 were identified. Most patients (87.5%) exhibited classic phenotype with intellectual deficiency (41.7%), epilepsy (75%) or movement disorder (29%) as initial symptoms at a medium age of 7.5 months, but diagnostic was delayed in most cases (median age at diagnostic 8 years 5 months). Sensitivity to fasting or exertion in combination with those 3 main symptoms were the main differences between mutated and negative patients (p < 0.001). Patients with myoclonic seizures (52%) evolved with more severe intellectual deficiency and movement disorders compared with those with Early Onset Absence Epilepsy (38%). Three patients evolved from a classic phenotype during early childhood to a movement disorder predominant phenotype at a late childhood/adulthood. Conclusions Our data confirm that the classic phenotype is the most frequent in GLUT1DS. Myoclonic seizures are a distinctive feature of severe forms. However a great variability among patients and overlapping through life from milder classic phenotype to paroxysmal-prominent- movement-disorder phenotype are possible, thus making it difficult to identify definite genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]
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- 2015
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16. Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children.
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Gitiaux, Cyril, Simonnet, Hina, Eisermann, Monika, Leunen, Dorothee, Dulac, Olivier, Nabbout, Rima, Chevignard, Mathilde, Honnorat, Jerôme, Gataullina, Svetlana, Musset, Lucile, Scalais, Emmanuel, Gauthier, Agnès, Hully, Marie, Boddaert, Nathalie, Kuchenbuch, Mathieu, Desguerre, Isabelle, and Kaminska, Anna
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ANTI-NMDA receptor encephalitis , *PEDIATRIC diagnosis , *THETA rhythm , *EYE movement disorders , *NEUROPHYSIOLOGY , *GENE expression , *NEURAL transmission - Abstract
Highlights: [•] Abundant theta and alpha band rhythms in non-rapid eye movement (NREM) sleep represent a suggestive EEG pattern of anti-NMDA receptor encephalitis in pediatric patients. [•] Preserved background activity over at least one hemisphere in the awake state and in sleep were correlated with milder clinical expression. [•] The disruption of NMDA neurotransmission may lead to decrease of the slow waves component in the NREM sleep. [Copyright &y& Elsevier]
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- 2013
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17. Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination
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Efthymiou, S., Salpietro, V., Malintan, N., Poncelet, M., Kriouile, Y., Fortuna, S., Zorzi, R. de, Payne, K., Henderson, L.B., Cortese, A., Maddirevula, S., Alhashmi, N., Wiethoff, S., Ryten, M., Botia, J.A., Provitera, V., Schuelke, M., Vandrovcova, J., Groppa, S., Karashova, B.M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Goraya, J.S., Sultan, T., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M.D., Maagdenberg, A.M.J.M. van den, Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A.M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B.M., Boles, R., Papacostas, S., Vikelis, M., Rothman, J., Kullmann, D., Papanicolaou, E.Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N.N., Atawneh, O., Lim, S.Y., Shaikh, F., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y.A., Minetti, C., Al-Khawaja, I., Al-Mutairi, F., Hamed, S., Pipis, M., Bettencourt, C., Rinaldi, S., Walsh, L., Torti, E., Iodice, V., Najafi, M., Karimiani, E.G., Maroofian, R., Siquier-Pernet, K., Boddaert, N., Lonlay, P. de, Cantagrel, V., Aguennouz, M., Khorassani, M. el, Schmidts, M., Alkuraya, F.S., Edvardson, S., Nolano, M., Devaux, J., Houlden, H., SYNAPS Study Grp, Efthymiou, S., Salpietro, V., Malintan, N., Poncelet, M., Kriouile, Y., Fortuna, S., De Zorzi, R., Payne, K., Henderson, L. B., Cortese, A., Maddirevula, S., Alhashmi, N., Wiethoff, S., Ryten, M., Botia, J. A., Provitera, V., Schuelke, M., Vandrovcova, J., Walsh, L., Torti, E., Iodice, V., Najafi, M., Karimiani, E. G., Maroofian, R., Siquier-Pernet, K., Boddaert, N., De Lonlay, P., Cantagrel, V., Aguennouz, M., El Khorassani, M., Schmidts, M., Alkuraya, F. S., Edvardson, S., Nolano, M., Devaux, J., Houlden, H., Groppa, S., Karashova, B. M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Goraya, J. S., Sultan, T., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M. D., Van Den Maagdenberg, A. M. J. M., Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A. M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B. M., Boles, R., Papacostas, S., Vikelis, M., Rothman, J., Kullmann, D., Papanicolaou, E. Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N. N., Atawneh, O., Lim, S. -Y., Shaikh, F., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y. A., Minetti, C., Al-Khawaja, I., Al-Mutairi, F., Hamed, S., Pipis, M., Bettencourt, C., Rinaldi, S., Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratory of Molecular Biophysics, Department of Biochemistry, Department of Biochemistry, Hertie Institute for Clinical Brain Research and Center for Neurology, University of Tübingen, Department of Medical and Molecular Genetics, King‘s College London, Department of Human Genetics, Ruhr University Bochum (RUB), Universitat de Barcelona (UB), Fondazione, Leiden University Medical Center (LUMC), Department of Physiology and Cellular Biophysics [New York, NY, USA], Columbia University College of Physicians and Surgeons, Department of Microbiology, Università degli studi di Catania [Catania], Institut de Myologie, 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), Ceinge, centro di Ingegneria Genetica e Biotecnologie Avanzate, Unité des troubles du sommeil, Centre de référence national sur les maladies rares (narcolepsie, hypersomnie idiopathique, syndrome de Kleine-Levin)-Hôpital Gui-de-Chauliac, Muscular and Neurodegenerative Disease Unit, University of Genoa (UNIGE), Department of Molecular Neuroscience, University College of London [London] (UCL)-Institute of Neurology, Indiana University, Indiana University [Bloomington], Indiana University System-Indiana University System, Molecular and Clinical Sciences Institute - St George’s [London, UK] (Genetics Research Centre), University of London [London], 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 National de la Recherche Scientifique (CNRS), Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service métabolisme, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-CHU Necker - Enfants Malades [AP-HP], Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Efthymiou S., Salpietro V., Malintan N., Poncelet M., Kriouile Y., Fortuna S., De Zorzi R., Payne K., Henderson L.B., Cortese A., Maddirevula S., Alhashmi N., Wiethoff S., Ryten M., Botia J.A., Provitera V., Schuelke M., Vandrovcova J., Walsh L., Torti E., Iodice V., Najafi M., Karimiani E.G., Maroofian R., Siquier-Pernet K., Boddaert N., De Lonlay P., Cantagrel V., Aguennouz M., El Khorassani M., Schmidts M., Alkuraya F.S., Edvardson S., Nolano M., Devaux J., Houlden H., Groppa S., Karashova B.M., Nachbauer W., Boesch S., Arning L., Timmann D., Cormand B., Perez-Duenas B., Goraya J.S., Sultan T., Mine J., Avdjieva D., Kathom H., Tincheva R., Banu S., Pineda-Marfa M., Veggiotti P., Ferrari M.D., Van Den Maagdenberg A.M.J.M., Verrotti A., Marseglia G., Savasta S., Garcia-Silva M., Ruiz A.M., Garavaglia B., Borgione E., Portaro S., Sanchez B.M., Boles R., Papacostas S., Vikelis M., Rothman J., Kullmann D., Papanicolaou E.Z., Dardiotis E., Maqbool S., Ibrahim S., Kirmani S., Rana N.N., Atawneh O., Lim S.-Y., Shaikh F., Koutsis G., Breza M., Mangano S., Scuderi C., Morello G., Stojkovic T., Zollo M., Heimer G., Dauvilliers Y.A., Minetti C., Al-Khawaja I., Al-Mutairi F., Hamed S., Pipis M., Bettencourt C., Rinaldi S., Efthymiou, Stephanie, Salpietro, Vincenzo, Malintan, Nancy, Poncelet, Mallory, Kriouile, Yamna, Fortuna, Sara, De Zorzi, Rita, Payne, Katelyn, Henderson, Lindsay B, Cortese, Andrea, Maddirevula, Sateesh, Alhashmi, Nadia, Wiethoff, Sarah, Ryten, Mina, Botia, Juan A, Provitera, Vincenzo, Schuelke, Marku, Vandrovcova, Jana, Walsh, Laurence, Torti, Erin, Iodice, Valeria, Najafi, Maryam, Karimiani, Ehsan Ghayoor, Maroofian, Reza, Siquier-Pernet, Karine, Boddaert, Nathalie, De Lonlay, Pascale, Cantagrel, Vincent, Aguennouz, Mhammed, El Khorassani, Mohamed, Schmidts, Miriam, Alkuraya, Fowzan S, Edvardson, Simon, Nolano, Maria, Devaux, Jérôme, Houlden, Henry, 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) (APHP)-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 la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)
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Male ,[SDV]Life Sciences [q-bio] ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Nerve Fibers, Myelinated ,Gene Frequency ,Neurodevelopmental Disorder ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Nerve Growth Factor ,Protein Isoforms ,Child ,ComputingMilieux_MISCELLANEOUS ,Myelin Sheath ,neurofascin ,neurodevelopment ,peripheral demyelination ,Allele ,Demyelinating Disease ,Genomics ,neurodevelopment, neurofascin, peripheral demyelination ,Settore MED/39 - Neuropsichiatria Infantile ,Pedigree ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Child, Preschool ,Peripheral Nerve ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,Neuroglia ,Human ,Adult ,Adolescent ,Nervous System Malformations ,Guillain-Barre Syndrome ,Axon ,Nervous System Malformation ,Ranvier's Nodes ,Humans ,Nerve Growth Factors ,Peripheral Nerves ,Alleles ,Autoantibodies ,Infant ,Protein Isoform ,Original Articles ,Axons ,nervous system ,Neurodevelopmental Disorders ,Cell Adhesion Molecule ,Mutation ,Cell Adhesion Molecules ,Demyelinating Diseases - Abstract
See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees of central and peripheral involvement. Abnormal expression of Nfasc155 is accompanied by severe loss of myelinated fibres., Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function.
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- 2019
18. Type I interferon-mediated autoinflammation due to DNase II deficiency
- Author
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Flavio Faletra, Gabriele Stocco, Evelyn Hartmann, Chantal Brouzes, Flavia Guillem, Fabrice Porcheray, Florence Uettwiller, Carolina Uggenti, Diego Vozzi, Marion Rabant, Capucine Picard, Nicolas Cagnard, Elisa Piscianz, Olivier Hermine, Andrea Taddio, Sophie Candon, Gunther Hartmann, Leo A. H. Zeef, Pierre Quartier, Marie Alexandra Alyanakian, Brigitte Bader-Meunier, Benoit Beitz, Gillian I. Rice, Muriel Girard, Monique Fabre, Alberto Tommasini, Dominique Lasne, Marine Depp, Nathalie Boddaert, Mathieu P Rodero, Stefano Volpi, Marco Gattorno, Yanick J. Crow, Eva Bartok, Michael Dussiot, Michel Polak, Tiffany Pascreau, Roberta Caorsi, Erika Della Mina, Naoki Kitabayashi, Annalisa Marcuzzi, Vincent Bondet, Paolo Picco, Luis Seabra, Jacques Beltrand, Erica Valencic, Marie-Louise Frémond, Bénédicte Neven, Frédéric Rieux-Laucat, Darragh Duffy, Alessandra Tesser, Patrick Nitschke, Anna Monica Bianco, Marina Charbit, Annie Harroche, Serena Pastore, Winfried Barchet, Laboratory of neurogenetics and neuroinflammation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Trieste, University of Bonn, Academic Unit of Medical Genetic, University of Manchester [Manchester], Microbiology Technology Institute, BIOASTER Microbiology Technology Institute [Lyon], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Giannina Gaslini Institute, Istituto Giannina Gaslini, Genova, Immunologia Clinica e Sperimentale, Service d'immuno-hématologie pédiatrique [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 Radiologie et imagerie médicale [CHU Necker], Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Service de néphrologie pédiatrique [CHU Necker], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Centre d'étude des Déficits Immunitaires, Service d'endocrinologie, gynécologie et diabétologie pédiatriques [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), Department of Life Sciences, Institute of Clinical Chemistry and Pharmacology, Center for Integrated Oncology, University Hospital of Bonn, Service d'Hématologie Adulte, IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy, Y.J.C. acknowledges the European Research Council (GA 309449), and a state subsidymanaged by the National Research Agency (France) under the 'Investments for the Future'program bearing the reference ANR-10-IAHU-01. We thank ImmunoQure AGfor sharing of antibodies used to assess interferon alpha protein levels in the Simoa assay.M.-L.F. is supported by the Institut National de la Santé et de la Recherche Médicale(Grant number 000427993). A.T. and M.G. acknowledge the Italian Telethon (Grant no.GGP15241A). A.T. acknowledges the Institute for Maternal and Child Health-IRCCS'Burlo Garofolo' (RC 17/2014 funded by Italian Ministry of Health, art 12 and 12bis D.lgs 502/92), the 'Associazione Azzurra Malattie Rare'and the 'Beneficientia Stiftung in Vaduz'. We would like to thank Olivier pellet and Jerome Megret from theflow cytometry platform at SFR Necker (INSERM US24-CNRS UMS 3633) for their help withperipheral blood mononuclear cell subset isolation. We would like to thank the Geno-mics Platform, INSERM UMR1163 for whole-exome sequencing. E.B., G.H., and W.B.acknowledge DZIF funding and German Research Foundation (DFG) grants EXC1023:ImmunoSensation, CRCs 670 and 704, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 309449,EC:FP7:ERC,ERC-2012-StG_20111109,T1-IFN(2013), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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 du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), BIOASTER, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Trieste = University of Trieste, Universität Bonn = University of Bonn, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital Bonn, Vougny, Marie-Christine, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Definition and characterization of type I interferonopathies - T1-IFN - - EC:FP7:ERC2013-03-01 - 2018-02-28 - 309449 - VALID, Rodero, Mathieu P., Tesser, Alessandra, Bartok, Eva, Rice, Gillian I., Della Mina, Erika, Depp, Marine, Beitz, Benoit, Bondet, Vincent, Cagnard, Nicola, Duffy, Darragh, Dussiot, Michael, Frã©mond, Marie-Louise, Gattorno, Marco, Guillem, Flavia, Kitabayashi, Naoki, Porcheray, Fabrice, Rieux-Laucat, Frederic, Seabra, Lui, Uggenti, Carolina, Volpi, Stefano, Zeef, Leo A. H., Alyanakian, Marie-Alexandra, Beltrand, Jacque, Bianco, Anna Monica, Boddaert, Nathalie, Brouzes, Chantal, Candon, Sophie, Caorsi, Roberta, Charbit, Marina, Fabre, Monique, Faletra, Flavio, Girard, Muriel, Harroche, Annie, Hartmann, Evelyn, Lasne, Dominique, Marcuzzi, Annalisa, Neven, Bã©nã©dicte, Nitschke, Patrick, Pascreau, Tiffany, Pastore, Serena, Picard, Capucine, Picco, Paolo, Piscianz, Elisa, Polak, Michel, Quartier, Pierre, Rabant, Marion, Stocco, Gabriele, Taddio, Andrea, Uettwiller, Florence, Valencic, Erica, Vozzi, Diego, Hartmann, Gunther, Barchet, Winfried, Hermine, Olivier, Bader-Meunier, Brigitte, Tommasini, Alberto, and Crow, Yanick J.
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Genetics and Molecular Biology (all) ,Male ,0301 basic medicine ,Erythroblasts ,[SDV]Life Sciences [q-bio] ,DNASE2 ,type I interferon ,autoinflammation ,exome sequencing ,Up-Regulation/drug effects ,General Physics and Astronomy ,Erythroblasts/immunology ,DNASE2, type I interferon, autoinflammation, exome sequencing ,Biochemistry ,LS3_11 ,0302 clinical medicine ,Interferon ,Interferon-alpha/blood ,Membranoproliferative glomerulonephritis ,STAT1 ,Phosphorylation ,lcsh:Science ,Child ,ComputingMilieux_MISCELLANEOUS ,Deoxyribonucleases ,Multidisciplinary ,biology ,RNA, Messenger/analysis ,Chemistry (all) ,Endodeoxyribonucleases/deficiency ,Up-Regulation ,3. Good health ,STAT1 Transcription Factor ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,STAT1 Transcription Factor/metabolism ,Antibody ,Signal Transduction ,medicine.drug ,STAT3 Transcription Factor ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Adolescent ,Science ,Alpha interferon ,Antiviral Agents/pharmacology ,Hematopoiesis/immunology ,Antiviral Agents ,Article ,General Biochemistry, Genetics and Molecular Biology ,Deoxyribonucleases/deficiency ,NO ,Physics and Astronomy (all) ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Humans ,RNA, Messenger ,Signal Transduction/immunology ,Endodeoxyribonucleases ,Innate immune system ,Sequence Analysis, RNA ,Gene Expression Profiling ,Hereditary Autoinflammatory Diseases ,Interferon-alpha ,General Chemistry ,medicine.disease ,Hematopoiesis ,030104 developmental biology ,STAT3 Transcription Factor/metabolism ,Hereditary Autoinflammatory Diseases/blood ,Mutation ,Immunology ,biology.protein ,Nucleic acid ,lcsh:Q ,Biochemistry, Genetics and Molecular Biology (all) ,030215 immunology - Abstract
Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans., Nucleic acid sensing is important to ensure that an innate immune response is only mounted against microbial nucleic acid. Here, the authors identify loss-of-function mutations in the DNASE2 gene that cause type I interferon-mediated autoinflammation due to enhanced systemic interferon signaling.
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- 2017
19. Moyamoya syndrome in children with neurofibromatosis type 1: Italian-French experience
- Author
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Giulio Piluso, Marco Pavanello, Giuseppe Mirone, Silverio Perrotta, Dominique Vidaud, Federico Di Rocco, Teresa Giugliano, Valeria Capra, Nathalie Boddaert, Mario Cirillo, Michel Zerah, Claudia Santoro, Bruno Nobili, Stanislas Lyonnet, Manoelle Kossorotoff, Raphael Calmon, Armando Cama, Alessandra D'Amico, Giuseppe Cinalli, Santoro, Claudia, Rocco, Federico Di, Kossorotoff, Manoelle, Zerah, Michel, Boddaert, Nathalie, Calmon, Raphael, Vidaud, Dominique, Cirillo, Mario, Cinalli, Giuseppe, Mirone, Giuseppe, Giugliano, Teresa, Piluso, Giulio, D'Amico, Alessandra, Capra, Valeria, Pavanello, Marco, Cama, Armando, Nobili, Bruno, Lyonnet, Stanisla, and Perrotta, Silverio
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0301 basic medicine ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Neurofibromatosis 1 ,Adolescent ,Genotype ,Neuroimaging ,neurofibromatosis type 1 ,Magnetic resonance angiography ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,cancer ,Humans ,Moyamoya disease ,Neurofibromatosis ,Child ,neoplasms ,Genetics (clinical) ,Neurofibromin 1 ,medicine.diagnostic_test ,Base Sequence ,moyamoya syndrome ,business.industry ,Cerebral infarction ,magnetic resonance angiography ,organic chemicals ,fungi ,Infant, Newborn ,Cancer ,Infant ,Magnetic resonance imaging ,Mean age ,medicine.disease ,Magnetic Resonance Imaging ,nervous system diseases ,030104 developmental biology ,Italy ,Child, Preschool ,Cohort ,Female ,France ,Moyamoya Disease ,business ,030217 neurology & neurosurgery - Abstract
Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.
- Published
- 2016
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