Accéder directement au contenu Accéder directement à la navigation
Nouvelle interface
Article dans une revue

A framework to identify contributing genes in patients with Phelan-McDermid syndrome

Anne-Claude Tabet 1, 2, 3 Thomas Rolland 2, 3 Marie Ducloy 2, 3 Jonathan Levy 1 Julien Buratti 2, 3 Alexandre Mathieu 2, 3 Damien Haye 1 Laurence Perrin 1 Céline Dupont 1 Sandrine Passemard 1 Yline Capri 1 Alain Verloes 1 Séverine Drunat 1 Boris Keren 4 Cyril Mignot 5 Isabelle Marey 5 Aurélia Jacquette 5 Sandra Whalen 5 Jean Pipiras 6 Jean Benzacken 6 Sandra Chantot-Bastaraud 7 Alexandra Afenjar 8 Delphine Heron 8 Cédric Le Caignec 9 Claire Beneteau 9 Olivier Pichon 9 Bertrand Isidor 9 Albert David 9 Laïla El Khattabi 10 Stephan Kemeny 11 Laetitia Gouas 11 Philippe Vago 11 Anne-Laure Mosca-Boidron 12 Laurence Faivre 13 Chantal Missirian 14 Nicole Philip 14 Damien Sanlaville 15 Patrick Edery 16 Véronique Satre 17 Charles Coutton 17 Françoise Devillard 17 Klaus Dieterich 17 Marie-Laure Vuillaume 18 Caroline Rooryck 18 Didier Lacombe 18 Lucile Pinson 19 Vincent Gatinois 19 Jacques Puechberty 19 Jean Chiesa 20, 21 James Lespinasse 22 Christèle Dubourg 23 Chloé Quélin 23 Mélanie Fradin 23 Hubert Journel 24 Annick Toutain 25 Dominique Martin-Coignard 26 Abdelamdjid Benmansour 1 Claire Leblond 2, 3 Roberto Toro 2, 3 Fréderique Amsellem 27 Richard Delorme 2, 3, 27 Thomas Bourgeron 2, 3 
Abstract : Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability (ID), absent or delayed speech, and autism spectrum disorders (ASD). It results from a deletion of the distal part of chromosome 22q13 that in most cases includes theSHANK3gene.SHANK3is considered a major gene for PMS, but the factors that modulate the severity of the syndrome remain largely unknown. In this study, we investigated 85 patients with different 22q13 rearrangements (78 deletions and 7 duplications). We first explored the clinical features associated with PMS, and provide evidence for frequent corpus callosum abnormalities in 28% of 35 patients with brain imaging data. We then mapped several candidate genomic regions at the 22q13 region associated with high risk of clinical features, and suggest a second locus at 22q13 associated with absence of speech. Finally, in some cases, we identified additional clinically relevant copy-number variants (CNVs) at loci associated with ASD, such as 16p11.2 and 15q11q13, which could modulate the severity of the syndrome. We also report an inheritedSHANK3deletion transmitted to five affected daughters by a mother without ID nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of patients with PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.
Liste complète des métadonnées

Littérature citée [53 références]  Voir  Masquer  Télécharger
Contributeur : Anthony Herrada Connectez-vous pour contacter le contributeur
Soumis le : mardi 20 mars 2018 - 17:57:51
Dernière modification le : mardi 18 octobre 2022 - 11:36:04


A framework to identify contri...
Publication financée par une institution


Distributed under a Creative Commons Paternité 4.0 International License



Anne-Claude Tabet, Thomas Rolland, Marie Ducloy, Jonathan Levy, Julien Buratti, et al.. A framework to identify contributing genes in patients with Phelan-McDermid syndrome. Genomic Medicine, 2017, 2, pp.32. ⟨10.1038/s41525-017-0035-2⟩. ⟨hal-01738521⟩



Consultations de la notice


Téléchargements de fichiers