Search

Your search keyword '"Khau Van Kien P"' showing total 133 results
Start Over Author "Khau Van Kien P"
133 results on '"Khau Van Kien P"'

1. Health-related quality of life in children and adolescents with Marfan syndrome or related disorders: a controlled cross-sectional study

Author

Thomas Edouard, Marie-Christine Picot, Fernanda Bajanca, Helena Huguet, Aitor Guitarte, Maud Langeois, Bertrand Chesneau, Philippe Khau Van Kien, Eric Garrigue, Yves Dulac, and Pascal Amedro

Subjects
Marfan syndrome, Health-related quality of life, Aerobic physical fitness, Peak oxygen consumption, Physical well-being, Psychological well-being, Medicine
Abstract

Abstract Background This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson’s or Spearman’s coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group. Results Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy. Conclusions This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients. Trial registration ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.

Published
2024
Full Text
View/download PDF

4. Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals

Author

Margot, Henri, Boursier, Guilaine, Duflos, Claire, Sanchez, Elodie, Amiel, Jeanne, Andrau, Jean-Christophe, Arpin, Stéphanie, Brischoux-Boucher, Elise, Boute, Odile, Burglen, Lydie, Caille, Charlotte, Capri, Yline, Collignon, Patrick, Conrad, Solène, Cormier-Daire, Valérie, Delplancq, Geoffroy, Dieterich, Klaus, Dollfus, Hélène, Fradin, Mélanie, Faivre, Laurence, Fernandes, Helder, Francannet, Christine, Gatinois, Vincent, Gerard, Marion, Goldenberg, Alice, Ghoumid, Jamal, Grotto, Sarah, Guerrot, Anne-Marie, Guichet, Agnès, Isidor, Bertrand, Jacquemont, Marie-Line, Julia, Sophie, Khau Van Kien, Philippe, Legendre, Marine, Le Quan Sang, K. H., Leheup, Bruno, Lyonnet, Stanislas, Magry, Virginie, Manouvrier, Sylvie, Martin, Dominique, Morel, Godelieve, Munnich, Arnold, Naudion, Sophie, Odent, Sylvie, Perrin, Laurence, Petit, Florence, Philip, Nicole, Rio, Marlène, Robbe, Julie, Rossi, Massimiliano, Sarrazin, Elisabeth, Toutain, Annick, Van Gils, Julien, Vera, Gabriella, Verloes, Alain, Weber, Sacha, Whalen, Sandra, Sanlaville, Damien, Lacombe, Didier, Aladjidi, Nathalie, and Geneviève, David

Published
2020
Full Text
View/download PDF

5. A +3 variant at a donor splice site leads to a skipping of the MYH11 exon 32, a recurrent RNA defect causing Heritable Thoracic Aortic Aneurysm and Dissection and/or Patent Ductus Arteriosus

Author

Bertrand Chesneau, Aurélie Plancke, Guillaume Rolland, Bertrand Marcheix, Yves Dulac, Thomas Edouard, Julie Plaisancié, Marion Aubert‐Mucca, Sophie Julia, Maud Langeois, Thierry Lavabre‐Bertrand, and Philippe Khau Van Kien

Subjects
genotype–phenotype correlation, heritable aortic aneurysm syndrome, MYH11, patent ductus arteriosus, splicing, Genetics, QH426-470
Abstract

Abstract Background Pathogenic variants in MYH11 are associated with either heritable thoracic aortic aneurysm and dissection (HTAAD), patent ductus arteriosus (PDA) syndrome, or megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS). Methods and Results We report a family referred for molecular diagnosis with HTAAD/PDA phenotype in which we found a variant at a non‐conserved position of the 5’ donor splice site of intron 32 of MYH11 potentially altering splicing (NM_002474.3:c.4578+3A>C). Although its cosegregation with disease was observed, it remained of unknown significance. Later, aortic surgery in the proband gave us the opportunity to perform a transcript analysis. This showed a skipping of the exon 32, an RNA defect previously reported to be translated to an in‐frame loss of 71 amino acids and a dominant‐negative effect in the smooth muscle myosin rod. This RNA defect is also reported in 3 other HTAAD/PDA pedigrees. Conclusion This report confirms that among rare variants in MYH11, skipping of exon 32 is recurrent. This finding is of particular interest to establish complex genotype–phenotype correlations where some alleles are associated with autosomal dominant HTAAD/PDA, while others result in recessive or dominant visceral myopathies.

Published
2021
Full Text
View/download PDF

6. Clinical and genetic data of 22 new patients with SMAD3 pathogenic variants and review of the literature

Author

Bertrand Chesneau, Thomas Edouard, Yves Dulac, Hélène Colineaux, Maud Langeois, Nadine Hanna, Catherine Boileau, Pauline Arnaud, Nicolas Chassaing, Sophie Julia, Guillaume Jondeau, Aurélie Plancke, Philippe Khau Van Kien, and Julie Plaisancié

Subjects
Aneurysms‐Osteoarthritis syndrome, Loeys–Dietz syndrome, SMAD3, TGFβ, Genetics, QH426-470
Abstract

Abstract Background Pathogenic SMAD3 variants are responsible for a cardiovascular phenotype, mainly thoracic aortic aneurysms and dissections. Precocious identification of the vascular risk such as aortic dilatation in mutated patients has a major impact in terms of management, particularly to avoid dissection and sudden death. These vascular damages are classically associated with premature osteoarthritis and skeletal abnormalities. However, variable expressivity and incomplete penetrance are common with SMAD3 variants. Methods To investigate the clinical variability observed within SMAD3 patients, we reviewed the phenotypic and genetic data of 22 new patients from our Centre and of 133 patients reported in the literature. From this cohort of 155 mutated individuals, we first aimed to delineate an estimated frequency of the main clinical signs associated with SMAD3 pathogenic variants and, then, to look for genotype‐phenotype correlations, mainly to see if the aortic phenotype (AP) could be predicted by the SMAD3 variant type. Results We showed, herein, the absence of correlation between the SMAD3 variant type and the occurrence of an AP in patients. Conclusion Therefore, this report brings additional data for the genotype‐phenotype correlations of SMAD3 variants and the need to explore in more detail the effects of genetic modifiers that could influence the phenotype.

Published
2020
Full Text
View/download PDF

8. NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients

Author

Bertacchi, Michele, Romano, Anna Lisa, Loubat, Agnès, Tran Mau‐Them, Frederic, Willems, Marjolaine, Faivre, Laurence, Khau van Kien, Philippe, Perrin, Laurence, Devillard, Françoise, Sorlin, Arthur, Kuentz, Paul, Philippe, Christophe, Garde, Aurore, Neri, Francesco, Di Giaimo, Rossella, Oliviero, Salvatore, Cappello, Silvia, D'Incerti, Ludovico, Frassoni, Carolina, and Studer, Michèle

Published
2020
Full Text
View/download PDF

9. Single Circulating Fetal Trophoblastic Cells Eligible for Non Invasive Prenatal Diagnosis: the Exception Rather than the Rule

Author

Cayrefourcq, Laure, Vincent, Marie-Claire, Pierredon, Sandra, Moutou, Céline, Imbert-Bouteille, Marion, Haquet, Emmanuelle, Puechberty, Jacques, Willems, Marjolaine, Liautard-Haag, Cathy, Molinari, Nicolas, Zordan, Cécile, Dorian, Virginie, Rooryck-Thambo, Caroline, Goizet, Cyril, Chaussenot, Annabelle, Rouzier, Cécile, Boureau-Wirth, Amandine, Monteil, Laetitia, Calvas, Patrick, Miry, Claire, Favre, Romain, Petrov, Yuliya, Khau Van Kien, Philippe, Le Boette, Elsa, Fradin, Mélanie, Alix-Panabières, Catherine, and Guissart, Claire

Published
2020
Full Text
View/download PDF

10. OTX2duplications: a recurrent cause of oculo-auriculo-vertebral spectrum

Author

Celse, Tristan, Tingaud-Sequeira, Angèle, Dieterich, Klaus, Siegfried, Geraldine, Lecaignec, Cédric, Bouneau, Laurence, Fannemel, Madeleine, Salaun, Gaelle, Laffargue, Fanny, Martinez, Guillaume, Satre, Véronique, Vieville, Gaelle, Bidart, Marie, Soussi Zander, Cecilia, Turesson, Ann-Charlotte, Splitt, Miranda, Reboul, Dorothee, Chiesa, Jean, Khau Van Kien, Philippe, Godin, Manon, Gruchy, Nicolas, Goel, Himanshu, Palmer, Elizabeth, Demetriou, Kalliope, Shalhoub, Carolyn, Rooryck, Caroline, and Coutton, Charles

Abstract

BackgroundOculo-auriculo-vertebral spectrum (OAVS) is the second most common cause of head and neck malformations in children after orofacial clefts. OAVS is clinically heterogeneous and characterised by a broad range of clinical features including ear anomalies with or without hearing loss, hemifacial microsomia, orofacial clefts, ocular defects and vertebral abnormalities. Various genetic causes were associated with OAVS and copy number variations represent a recurrent cause of OAVS, but the responsible gene often remains elusive.MethodsWe described an international cohort of 17 patients, including 10 probands and 7 affected relatives, presenting with OAVS and carrying a 14q22.3 microduplication detected using chromosomal microarray analysis. For each patient, clinical data were collected using a detailed questionnaire addressed to the referring clinicians. We subsequently studied the effects of OTX2overexpression in a zebrafish model.ResultsWe defined a 272 kb minimal common region that only overlaps with the OTX2gene. Head and face defects with a predominance of ear malformations were present in 100% of patients. The variability in expressivity was significant, ranging from simple chondromas to severe microtia, even between intrafamilial cases. Heterologous overexpression of OTX2in zebrafish embryos showed significant effects on early development with alterations in craniofacial development.ConclusionsOur results indicate that proper OTX2dosage seems to be critical for the normal development of the first and second branchial arches. Overall, we demonstrated that OTX2genomic duplications are a recurrent cause of OAVS marked by auricular malformations of variable severity.

Published
2023
Full Text
View/download PDF

14. Maternally inherited duplication of the possible imprinted 14q31 region

Author

C Stavropoulou, M.-G. Mattei, Danielle Depetris, Cécile Mignon-Ravix, Khau Van Kien P, and Mugneret F

Subjects
Genetics, Monosomy, Karyotype, Biology, medicine.disease, Uniparental disomy, Gene duplication, medicine, Imprinting (psychology), Letters to the Editor, Genomic imprinting, Trisomy, Genetics (clinical), Chromosome 12
Abstract

The existence of parent of origin differences in the expression of some genes, a process known as genomic imprinting, has been recognised and documented over the past several years. This epigenetic marking process results in the differential expression of normal genes, depending on whether they are of maternal or paternal origin. A number of human disorders have been identified as resulting from alterations in genomic imprinting.1 One type of genetic abnormality which can unmask genomic imprinting is uniparental disomy (UPD), in which both chromosomes of one pair are inherited from one parent, with no contribution from the other.2 Distinct phenotypes exhibited by patients with maternal and paternal UPD(14) strongly suggest that at least some genes on human chromosome 14 are subject to imprinting effects.3-6 This finding is supported by studies in the mouse indicating that the distal portion of chromosome 12, recognised as a candidate imprinted region, is syntenic with human chromosome 14q.7 Nevertheless, no imprinted genes have yet been identified on chromosome 14, and the location of the imprinted region on human chromosome 14 remains unclear. Analysis of parental origin effects in human trisomy for chromosome 14q8 or monosomy for the same chromosome9makes the region 14q23-q32 a candidate region for containing imprinted genes.10 Moreover, the observation of a partial duplication of 14q in a developmentally delayed girl with minor abnormalities and her phenotypically normal father led Robin et al 11 to propose that the 14q24.3-q31 region may be imprinted. As genotype-phenotype correlations in patients with aneusomy for this region may help the identification of imprinted genes on human chromosome 14, we report here a direct 14q31 duplication observed in a child with mild developmental delay and his phenotypically normal mother. This duplication was also detected in five relatives with a normal …

Published
2001
Full Text
View/download PDF

16. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author

Callier , P., Aral , B., Hanna , N., Lambert , S., Dindy , H., Ragon , C., Payet , M., Collod-Béroud , Gwenaëlle, Carmignac , V., Delrue , M. A., Goizet , C., Philip , N., Busa , Tiffany, Dulac , Y., Missotte , I., Sznajer , Y., Toutain , A., Francannet , C., Megarbane , A., Julia , S., Edouard , T., Sarda , P., Amiel , J., Lyonnet , S., Cormier-Daire , V., Gilbert , B., Jacquette , A., Heron , D., Collignon , P., Lacombe , D., Morice-Picard , F., Jouk , P. S., Cusin , V., Willems , M., Sarrazin , E., Amarof , K., Coubes , C., Addor , M. C., Journel , H., Colin , E., Khau Van Kien , P., Baumann , C., Leheup , B., Martin-Coignard , D., Doco-Fenzy , M., Goldenberg , A., Plessis , G., Thevenon , J., Pasquier , L., Odent , S., Vabres , P., Huet , F., Marle , N., Mosca-Boidron , A. L., Mugneret , F., Gauthier , S., Binquet , C., Thauvin-Robinet , C., Jondeau , G., Boileau , C., Faivre , L., Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Ambroise Paré [AP-HP], Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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 génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre hospitalier territorial Gaston-Bourret [Nouméa], Cliniques Universitaires Saint-Luc [Bruxelles], Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Université Saint-Joseph de Beyrouth (USJ), Service Pédiatrique [Toulouse], CHU Toulouse [Toulouse]-Hôpital des Enfants, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Médicale [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), Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital intercommunal de Font-Pré, Département de génétique, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, 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), Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre hospitalier de Vannes, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Le Mans (CH Le Mans), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Pôle Enfants [CHU Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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 ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hôpital Ambroise Paré, 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 ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Hôpital Bretonneau-CHRU Tours, Université Saint-Joseph de Beyrouth ( USJ ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, 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 ), CHU de la Martinique, Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Université d'Angers ( UA ) -CHU Angers, Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), CHU Le MAns, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), 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), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hopital Necker-Enfants Malades, CHU de Poitiers, and Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Adult, Male, musculoskeletal diseases, Comparative Genomic Hybridization, congenital, hereditary, and neonatal diseases and abnormalities, [ SDV ] Life Sciences [q-bio], Adolescent, [SDV]Life Sciences [q-bio], Sequence Analysis, DNA, Middle Aged, Marfan Syndrome, [SDV] Life Sciences [q-bio], Young Adult, X Chromosome Inactivation, Child, Preschool, Intellectual Disability, Cytogenetic Analysis, Mutation, Humans, Female, Genetic Testing, Prospective Studies, Child
Abstract

International audience; The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

Published
2013
Full Text
View/download PDF

19. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, Faivre, L, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, and Faivre, L

Abstract

The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

Published
2013

21. Ischemic Digital Ulcers Affect Hand Disability and Pain in Systemic Sclerosis

Author

Mouthon, Luc, Carpentier, Patrick H., Lok, Catherine, Clerson, Pierre, Gressin, Virginie, Hachulla, Eric, Bérezné, Alice, Diot, Elisabeth, Khau Van Kien, Aurélie, Jego, Patrick, Agard, Christian, Duval-Modeste, Anne Bénédicte, Sparsa, Agnès, Puzenat, Eve, Richard, Marie-Aleth, Lok, C, Thuillier, D, Le Clec’h, C, Duchêne, F, Puzenat, E, Prey, S, Solanilla, A, Bourgault-Villada, I, Boulogne, Le Hello, C, Bienvenu, B, Berthier, S, Muller, G, Remond, B, Carpentier, P, Damade, R, Beneton-Benhard, N, Maillard, H, Barcat, D, Hachulla, E, Hatron, PY, Sparsa, A, Doffoel-Hantz, V, Fauchais, AL, Geffray, L, Coppéré, B, Jullien, D, Granier, F, Harle, JR, Granel, B, Richard, MA, Maurier, F, Cohen, JD, Khau Van Kien, A, Granel-Brocard, F, Agard, C, Queyrel, V, Corondan, A, Bérezné, A, Mouthon, L, Crickx, B, Picard Dahan, C, Eguia, B, Francès, C, Emmerich, J, Fiessinger, JN, Mathian, A, Lazareth, I, Michon-Pasturel, U, Viallard, JF, Wierzbicka-Hainaut, E, Fleuret, C, Léonard-Lefèbvre, F, Reguiai, Z, Jego, P, Perdriger, A, Modeste Duval, AB, Bonnin, A, Chatelus, E, Poindron, V, Diot, E, Bica-Chicinas, D, Roger, M, Wahl, D, and Zuily, S

Abstract

Objective.Ischemic digital ulcers (DU) are frequent and severe complications of systemic sclerosis (SSc). The purpose of our study was to assess the effect of DU on hand disability and pain in patients with SSc.Methods.The Evaluation of the Impact of Recurrent Ischemic DU on Hand Disability in Patients with SSc (ECLIPSE) is a prospective, multicenter, noninterventional study with a 2-year followup. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan therapy were included between October 2009 and March 2011. This cohort is described at the time of inclusion.Results.There were 190 patients (132 females) from 53 centers. Mean age ± SD was 43 ± 15 years at SSc diagnosis and 53 ± 15 years at inclusion. In 105 patients (56.2%), DU were the first non-Raynaud symptoms of SSc. The mean time interval between the occurrence of Raynaud phenomenon and the first DU episode was 6.6 ± 9.1 years. The mean numbers of active DU and fingers affected per patient for both hands were 2.3 ± 1.8 and 2.2 ± 1.6, respectively. Presence of active DU at inclusion was significantly associated with pain and impaired hand function: Visual Analog Scale for pain (0 to 10) was 6.2 ± 2.6 versus 2.5 ± 2.4 (p < 0.0001) and Cochin Hand Function Scale for hand disability (0 to 90) was 38 ± 20 versus 25 ± 19 (p < 0.0001), respectively.Conclusion.DU represent a major sign of SSc, often affecting multiple fingers and both hands. They are significantly associated with pain and hand disability.

Published
2014
Full Text
View/download PDF

22. Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing

Author

Kuentz, Paul, St-Onge, Judith, Duffourd, Yannis, Courcet, Jean-Benoît, Carmignac, Virginie, Jouan, Thibaud, Sorlin, Arthur, Abasq-Thomas, Claire, Albuisson, Juliette, Amiel, Jeanne, Amram, Daniel, Arpin, Stéphanie, Attie-Bitach, Tania, Bahi-Buisson, Nadia, Barbarot, Sébastien, Baujat, Geneviève, Bessis, Didier, Boccara, Olivia, Bonnière, Maryse, Boute, Odile, Bursztejn, Anne-Claire, Chiaverini, Christine, Cormier-Daire, Valérie, Coubes, Christine, Delobel, Bruno, Edery, Patrick, Chehadeh, Salima El, Francannet, Christine, Geneviève, David, Goldenberg, Alice, Haye, Damien, Isidor, Bertrand, Jacquemont, Marie-Line, Khau Van Kien, Philippe, Lacombe, Didier, Martin, Ludovic, Martinovic, Jelena, Maruani, Annabel, Mathieu-Dramard, Michèle, Mazereeuw-Hautier, Juliette, Michot, Caroline, Mignot, Cyril, Miquel, Juliette, Morice-Picard, Fanny, Petit, Florence, Phan, Alice, Rossi, Massimiliano, Touraine, Renaud, Verloes, Alain, Vincent, Marie, Vincent-Delorme, Catherine, Whalen, Sandra, Willems, Marjolaine, Marle, Nathalie, Lehalle, Daphné, Thevenon, Julien, Thauvin-Robinet, Christel, Hadj-Rabia, Smaïl, Faivre, Laurence, Vabres, Pierre, and Rivière, Jean-Baptiste

Abstract

Purpose:Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS.Methods:We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested.Results:We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03 × 10−5). We identified 40 different mutations and found strong oncogenic mutations more frequently in patients without brain overgrowth (50.6%) than in those with brain overgrowth (15.2%; P = 0.00055). Mutant allele levels were higher in skin and overgrown tissues than in blood and buccal samples (P = 3.9 × 10−25), regardless of the phenotype.Conclusion:Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions.Genet Med advance online publication 02 February 2017

Published
2017
Full Text
View/download PDF

23. Bi-allelic variants in COL3A1encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts

Author

Vandervore, Laura, Stouffs, Katrien, Tanyalcin, Ibrahim, Vanderhasselt, Tim, Roelens, Filip, Holder-Espinasse, Muriel, Jørgensen, Agnete, Pepin, Melanie G, Petit, Florence, Khau Van Kien, Philippe, Bahi-Buisson, Nadia, Lissens, Willy, Gheldof, Alexander, Byers, Peter H, and Jansen, Anna C

Abstract

BackgroundCollagens are one of the major constituents of the pial membrane, which plays a crucial role in neuronal migration and cortical lamination during brain development. Type III procollagen, the chains of which are encoded by COL3A1, is the ligand of the G protein-coupled receptor 56 (GPR56), also known as adhesion G protein-coupled receptor G1. Bi-allelic mutations in GPR56give rise to cobblestone-like malformation, white matter changes and cerebellar dysplasia. This report shows that bi-allelic mutations in COL3A1are associated with a similar phenotype.MethodsExome analysis was performed in a family consisting of two affected and two non-affected siblings. Brain imaging studies of this family and of two previously reported individuals with bi-allelic mutations in COL3A1were reviewed. Functional assays were performed on dermal fibroblasts.ResultsExome analysis revealed a novel homozygous variant c.145C>G (p.Pro49Ala) in exon 2 of COL3A1. Brain MRI in the affected siblings as well as in the two previously reported individuals with bi-allelic COL3A1mutations showed a brain phenotype similar to that associated with mutations in GPR56.ConclusionHomozygous or compound heterozygous mutations in COL3A1are associated with cobblestone-like malformation in all three families reported to date. The variability of the phenotype across patients suggests that genetic alterations in distinct domains of type III procollagen can lead to different outcomes. The presence of cobblestone-like malformation in patients with bi-allelic COL3A1mutations emphasises the critical role of the type III collagen–GPR56 axis and the pial membrane in the regulation of brain development and cortical lamination.

Published
2017
Full Text
View/download PDF

24. Genotype-phenotype correlation in 104 patients with vascular Ehlers-Danlos syndrome: Evidence for a mild form of the disease

Author

Bal, L., primary, Fauret, A.-L., additional, Ranque, B., additional, Frank, M., additional, Golmard, L., additional, Travers, C., additional, Khau Van Kien, P., additional, Denarié, N., additional, Messas, E., additional, Plauchu, H., additional, Germain, D., additional, Emmerich, J., additional, Fiessinger, J.-N., additional, and Jeunemaître, X., additional

Published
2011
Full Text
View/download PDF

25. Banques de données de mutations : enjeux et perspectives pour les maladies génétiques orphelines

Author

Humbertclaude, V., primary, Tuffery-Giraud, S., additional, Bareil, C., additional, Thèze, C., additional, Paulet, D., additional, Desmet, F.-O., additional, Hamroun, D., additional, Baux, D., additional, Girardet, A., additional, Collod-Béroud, G., additional, Khau Van Kien, P., additional, Roux, A.-F., additional, des Georges, M., additional, Béroud, C., additional, and Claustres, M., additional

Published
2010
Full Text
View/download PDF

27. Clinical and mutation-type analysis from an international series of 198 probands with a pathogenic FBN1 exons 24–32 mutation

Author

Faivre, L, primary, Collod-Beroud, G, additional, Callewaert, B, additional, Child, A, additional, Binquet, C, additional, Gautier, E, additional, Loeys, B L, additional, Arbustini, E, additional, Mayer, K, additional, Arslan-Kirchner, M, additional, Stheneur, C, additional, Kiotsekoglou, A, additional, Comeglio, P, additional, Marziliano, N, additional, Wolf, J E, additional, Bouchot, O, additional, Khau-Van-Kien, P, additional, Beroud, C, additional, Claustres, M, additional, Bonithon-Kopp, C, additional, Robinson, P N, additional, Adès, L, additional, De Backer, J, additional, Coucke, P, additional, Francke, U, additional, De Paepe, A, additional, Jondeau, G, additional, and Boileau, C, additional

Published
2008
Full Text
View/download PDF

35. Clinical and mutation-type analysis from an international series of 198 probands with a pathogenic FBN1 exons 24–32 mutation.

Author

Faivre, L., Collod-Beroud, G., Callewaert, B., Child, A., Binquet, C., Gautier, E., Loeys, B. .L, Arbustini, E., Mayer, K., Arslan-Kirchner, M., Stheneur, C., Kiotsekoglou, A., Comeglio, P., Marziliano, N., Wolf, J. E., Bouchot, O., Khau-Van-Kien, P., Beroud, C., Claustres, M., and Bonithon-Kopp, C.

Subjects
EXONS (Genetics), MARFAN syndrome, PHENOTYPES, GENETIC mutation, HETEROGENEITY
Abstract

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the spectrum is represented by neonatal MFS, the vast majority of probands carrying a mutation within exons 24–32. We previously showed that a mutation in exons 24–32 is predictive of a severe cardiovascular phenotype even in non-neonatal cases, and that mutations leading to premature truncation codons are under-represented in this region. To describe patients carrying a mutation in this so-called ‘neonatal’ region, we studied the clinical and molecular characteristics of 198 probands with a mutation in exons 24–32 from a series of 1013 probands with a FBN1 mutation (20%). When comparing patients with mutations leading to a premature termination codon (PTC) within exons 24–32 to patients with an in-frame mutation within the same region, a significantly higher probability of developing ectopia lentis and mitral insufficiency were found in the second group. Patients with a PTC within exons 24–32 rarely displayed a neonatal or severe MFS presentation. We also found a higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations. A high phenotypic heterogeneity could be described for recurrent mutations, ranging from neonatal to classical MFS phenotype. In conclusion, even if the exons 24–32 location appears as a major cause of the severity of the phenotype in patients with a mutation in this region, other factors such as the type of mutation or modifier genes might also be relevant.European Journal of Human Genetics (2009) 17, 491–501; doi:10.1038/ejhg.2008.207; published online 12 November 2008 [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

36. Axial spondylometaphyseal dysplasia: Confirmation and further delineation of a new SMD with retinal dystrophyHow to cite this article: Isidor B, Baron S, Khau van Kien P, Bertrand AM, David A, Le Merrer M. 2010. Axial spondylometaphyseal dysplasia: Confirmation and further delineation of a new SMD with retinal dystrophy. Am J Med Genet Part A 152A:1550–1554.

Author

Isidor, Bertrand, Baron, Sabine, Khau van Kien, Philippe, Bertrand, AnneMarie, David, Albert, and Le Merrer, Martine

Abstract

This report describes two unrelated boys presenting with short stature, femoral metaphyseal abnormalities, platyspondyly, and retinitis pigmentosa. Patients share similar findings with cases described by Ehara et al. Ehara et al. 1997; Eur J Pediatr 156:627–630 described as axial spondylometaphyseal dysplasia. The presence of consanguinity in one of our patients further supports an autosomal recessive mode of inheritance of what, we believe, constitutes a separate and distinct entity. © 2010 WileyLiss, Inc.

Published
2010
Full Text
View/download PDF

37. Automatic Determination of Aortic Compliance With Cine-Magnetic Resonance Imaging

Author

LALANDE, ALAIN, KHAU VAN KIEN, PHILIPPE, SALVÉ, NICOLAS, BEN SALEM, DOURÏED, LEGRAND, LOUIS, MICHAEL WALKER, PAUL, WOLF, JEAN-ERIC, and BRUNOTTE, FRANÇOIS

Abstract

Lalande A, Khau van Kien P, Salvé N, et al. Automatic determination of aortic compliance with cine-magnetic resonance imaging An application of fuzzy logic theory. Invest Radiol 2002;37685–691.

Published
2002

43. Rappel des dépistages de l’anévrysme l’aorte par la Société française de médecine vasculaire (SFMV)

Author

Laroche, J.P., Böge, G., Brisot, D., Mestre, S., Nou, M., Zappulla, C., Tapon, M., Perez-Martin, A., Schuster, I., Dauzat, M., Khau van Kien, A., Galanaud, J.P., and Quéré, I.

Abstract

En 2012 et 2013, à l’initiative de la SFMV a été mise en place l’opération VESALE. Il s’agissait de réaliser un dépistage échographique de l’anévrysme de l’aorte abdominale. Ces opérations ont rassemblé 12 000 personnes, elles ont été réalisées sur une journée. Les critères retenus pour VESALE étaient ceux de la SFMV en 2012 et 2013 [1–3]. Nous n’avions pas retenu en 2013 ceux de la HAS qui excluaient les femmes ; or les femmes fumeuses présentent une forte prévalence d’anévrysme, les publications les plus récentes le démontrent, publications postérieures au rapport de la HAS.

Published
2014
Full Text
View/download PDF

44. Le contrôle des ulcères digitaux ischémiques au cours de la sclérodermie systémique est associé à un meilleur pronostic fonctionnel de la main

Author

Mouthon, L., Carpentier, P., Lok, C., Clerson, P., Gressin, V., Hachulla, E., Bérezné, A., Diot, A., Khau Van Kien, A., Jego, P., Agar, C., Modeste Duval, A.-B., Sparsa, A., Puzenat, E., and Richard, M.-A.

Abstract

Les ulcères digitaux ischémiques (UD) sont l’une des complications de la sclérodermie systémique (ScS) et participent au handicap fonctionnel de la main. L’objectif était d’évaluer l’impact du contrôle de la maladie ulcéreuse digitale à 1 an sur le handicap de la main et la qualité de vie chez des patients sous bosentan.

Published
2014
Full Text
View/download PDF

45. À qui revient le dépistage ultrasonique ?

Author

Laroche, J.P., Böge, G., Brisot, D., Mestre, S., Nou, M., Zappulla, C., Tapon, M., Perez-Martin, A., Schuster, I., Dauzat, M., Khau Van Kien, A., Galanaud, J.P., and Quéré, I.

Abstract

Le dépistage de certaines affections vasculaires est aujourd’hui du domaine des ultrasons. Voici ce qui est validé en 2014 : dépistage de l’anévrysme de l’aorte abdominale (échoscopie ou échographie), la mesure de l’index de pression de cheville pour le dépistage de l’artériopathie asymptomatique. On peut étendre le dépistage au « balayage carotidien et fémoral », dépistage de plaques mais acte non validé.

Published
2014
Full Text
View/download PDF

46. La capillaroscopie dans la maladie de Rendu-Osler

Author

Marnas, E., Khau van Kien-Wautot, A., Quere, I., Laroche, J.P., Lorcerie, B., and Riviere, S.

Abstract

La maladie de Rendu-Osler (MRO) est une génopathie vasculaire responsable d’épistaxis, de télangiectasies cutanéo-muqueuses et de malformations artério-veineuses viscérales.

Published
2014
Full Text
View/download PDF

48. OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum.

Author

Celse T, Tingaud-Sequeira A, Dieterich K, Siegfried G, Lecaignec C, Bouneau L, Fannemel M, Salaun G, Laffargue F, Martinez G, Satre V, Vieville G, Bidart M, Soussi Zander C, Turesson AC, Splitt M, Reboul D, Chiesa J, Khau Van Kien P, Godin M, Gruchy N, Goel H, Palmer E, Demetriou K, Shalhoub C, Rooryck C, and Coutton C

Subjects
Humans, Animals, Zebrafish genetics, DNA Copy Number Variations genetics, Otx Transcription Factors genetics, Goldenhar Syndrome genetics, Cleft Lip, Cleft Palate
Abstract

Background: Oculo-auriculo-vertebral spectrum (OAVS) is the second most common cause of head and neck malformations in children after orofacial clefts. OAVS is clinically heterogeneous and characterised by a broad range of clinical features including ear anomalies with or without hearing loss, hemifacial microsomia, orofacial clefts, ocular defects and vertebral abnormalities. Various genetic causes were associated with OAVS and copy number variations represent a recurrent cause of OAVS, but the responsible gene often remains elusive., Methods: We described an international cohort of 17 patients, including 10 probands and 7 affected relatives, presenting with OAVS and carrying a 14q22.3 microduplication detected using chromosomal microarray analysis. For each patient, clinical data were collected using a detailed questionnaire addressed to the referring clinicians. We subsequently studied the effects of OTX2 overexpression in a zebrafish model., Results: We defined a 272 kb minimal common region that only overlaps with the OTX2 gene. Head and face defects with a predominance of ear malformations were present in 100% of patients. The variability in expressivity was significant, ranging from simple chondromas to severe microtia, even between intrafamilial cases. Heterologous overexpression of OTX2 in zebrafish embryos showed significant effects on early development with alterations in craniofacial development., Conclusions: Our results indicate that proper OTX2 dosage seems to be critical for the normal development of the first and second branchial arches. Overall, we demonstrated that OTX2 genomic duplications are a recurrent cause of OAVS marked by auricular malformations of variable severity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
Full Text
View/download PDF

49. Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants: A multicenter retrospective case series.

Author

Lesieur-Sebellin M, Till M, Khau Van Kien P, Herve B, Bourgon N, Dupont C, Tabet AC, Barrois M, Coussement A, Loeuillet L, Mousty E, Ea V, El Assal A, Mary L, Jaillard S, Beneteau C, Le Vaillant C, Coutton C, Devillard F, Goumy C, Delabaere A, Redon S, Laurent Y, Lamouroux A, Massardier J, Turleau C, Sanlaville D, Cantagrel V, Sonigo P, Vialard F, Salomon LJ, and Malan V

Subjects
Adult, Calcium-Binding Proteins genetics, Chromosome Disorders genetics, Chromosomes, Human, Pair 6 genetics, Female, Humans, Membrane Proteins genetics, Phenotype, Pregnancy, Retrospective Studies, Trisomy genetics, Virulence genetics, Virulence physiology, Calcium-Binding Proteins analysis, Chromosome Disorders complications, Membrane Proteins analysis
Abstract

Objective: Terminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations., Method: We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants., Results: Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities., Conclusion: This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations., (© 2021 John Wiley & Sons Ltd.)

Published
2022
Full Text
View/download PDF

50. A +3 variant at a donor splice site leads to a skipping of the MYH11 exon 32, a recurrent RNA defect causing Heritable Thoracic Aortic Aneurysm and Dissection and/or Patent Ductus Arteriosus.

Author

Chesneau B, Plancke A, Rolland G, Marcheix B, Dulac Y, Edouard T, Plaisancié J, Aubert-Mucca M, Julia S, Langeois M, Lavabre-Bertrand T, and Khau Van Kien P

Subjects
Aortic Dissection pathology, Aortic Aneurysm, Thoracic pathology, Ductus Arteriosus, Patent pathology, Exons, Humans, Male, Mutation, RNA Splicing, Young Adult, Aortic Dissection genetics, Aortic Aneurysm, Thoracic genetics, Ductus Arteriosus, Patent genetics, Myosin Heavy Chains genetics, RNA Splice Sites
Abstract

Background: Pathogenic variants in MYH11 are associated with either heritable thoracic aortic aneurysm and dissection (HTAAD), patent ductus arteriosus (PDA) syndrome, or megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS)., Methods and Results: We report a family referred for molecular diagnosis with HTAAD/PDA phenotype in which we found a variant at a non-conserved position of the 5' donor splice site of intron 32 of MYH11 potentially altering splicing (NM&#95;002474.3:c.4578+3A>C). Although its cosegregation with disease was observed, it remained of unknown significance. Later, aortic surgery in the proband gave us the opportunity to perform a transcript analysis. This showed a skipping of the exon 32, an RNA defect previously reported to be translated to an in-frame loss of 71 amino acids and a dominant-negative effect in the smooth muscle myosin rod. This RNA defect is also reported in 3 other HTAAD/PDA pedigrees., Conclusion: This report confirms that among rare variants in MYH11, skipping of exon 32 is recurrent. This finding is of particular interest to establish complex genotype-phenotype correlations where some alleles are associated with autosomal dominant HTAAD/PDA, while others result in recessive or dominant visceral myopathies., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results