RT Journal Article
SR Electronic
T1 A framework to identify modifier genes in patients with Phelan-McDermid syndrome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 117978
DO 10.1101/117978
A1 Anne-Claude Tabet
A1 Thomas Rolland
A1 Marie Ducloy
A1 Jonathan Lévy
A1 Julien Buratti
A1 Alexandre Mathieu
A1 Damien Haye
A1 Laurence Perrin
A1 Céline Dupont
A1 Sandrine Passemard
A1 Yline Capri
A1 Alain Verloes
A1 Séverine Drunat
A1 Boris Keren
A1 Cyril Mignot
A1 Isabelle Marey
A1 Aurélia Jacquette
A1 Sandra Whalen
A1 Eva Pipiras
A1 Brigitte Benzacken
A1 Sandra Chantot-Bastaraud
A1 Alexandra Afenjar
A1 Delphine Héron
A1 Cédric Le Caignec
A1 Claire Beneteau
A1 Olivier Pichon
A1 Bertrand Isidor
A1 Albert David
A1 Jean-Michel Dupont
A1 Stephan Kemeny
A1 Laetitia Gouas
A1 Philippe Vago
A1 Anne-Laure Mosca-Boidron
A1 Laurence Faivre
A1 Chantal Missirian
A1 Nicole Philip
A1 Damien Sanlaville
A1 Patrick Edery
A1 Véronique Satre
A1 Charles Coutton
A1 Françoise Devillard
A1 Klaus Dieterich
A1 Marie-Laure Vuillaume
A1 Caroline Rooryck
A1 Didier Lacombe
A1 Lucile Pinson
A1 Vincent Gatinois
A1 Jacques Puechberty
A1 Jean Chiesa
A1 James Lespinasse
A1 Christèle Dubourg
A1 Chloé Quelin
A1 Mélanie Fradin
A1 Hubert Journel
A1 Annick Toutain
A1 Dominique Martin
A1 Abdelamdjid Benmansour
A1 Roberto Toro
A1 Frédérique Amsellem
A1 Richard Delorme
A1 Thomas Bourgeron
YR 2017
UL http://biorxiv.org/content/early/2017/03/18/117978.abstract
AB Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability, speech impairment, and autism spectrum disorders (ASD). It results from a deletion of the 22q13 locus that in most cases includes the SHANK3 gene. SHANK3 is considered a major gene for PMS, but the factors modulating the severity of the syndrome remain largely unknown. In this study, we investigated 85 PMS patients with different 22q13 rearrangements (78 deletions, 7 duplications). We first explored their clinical features and provide evidence for frequent corpus callosum abnormalities. We then mapped candidate genomic regions at the 22q13 locus associated with risk of clinical features, and suggest a second locus associated with absence of speech. Finally, in some cases, we identified additional rearrangements at loci associated with ASD, potentially modulating the severity of the syndrome. We also report the first SHANK3 deletion transmitted to five affected daughters by a mother without intellectual disability nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.