Skip to Main content Skip to Navigation
Journal articles

Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.

Dalila Pinto 1, 2, 3, 4, 5, 6 Elsa Delaby 7 Daniele Merico 8 Mafalda Barbosa 1, 2, 3 Alison Merikangas 9 Lambertus Klei 10 Bhooma Thiruvahindrapuram 8 Xiao Xu 1, 2, 3 Robert Ziman 8 Zhuozhi Wang 8 Jacob Vorstman 11 Ann Thompson 12 Regina Regan 13 Marion Pilorge 7 Giovanna Pellecchia 8 Alistair Pagnamenta 14 Bárbara Oliveira 15 Christian Marshall 8, 16 Tiago Magalhaes 13, 15, 17 Jennifer Lowe 18, 19 Jennifer Howe 8 Anthony Griswold 20 John Gilbert 20 Eftichia Duketis 21 Beth Dombroski 22, 23 Maretha de Jonge 11 Michael Cuccaro 20 Emily Crawford 24, 25 Catarina Correia 15 Judith Conroy 13 Inês Conceição 15 Andreas Chiocchetti 21, 26 Jillian Casey 13 Guiqing Cai 1, 2, 3 Christelle Cabrol 7 Nadia Bolshakova 9 Elena Bacchelli 27 Richard Anney 9 Steven Gallinger 28 Michelle Cotterchio 29 Graham Casey 30 Lonnie Zwaigenbaum 31 Kerstin Wittemeyer 32 Kirsty Wing 14 Simon Wallace 33 Herman van Engeland 11 Ana Tryfon 2, 3 Susanne Thomson 25, 24 Latha Soorya 2, 3 Bernadette Rogé 34 Wendy Roberts 35 Fritz Poustka 21 Susana Mouga 36, 37 Nancy Minshew 10 Alison Mcinnes 2, 3 Susan Mcgrew 38 Catherine Lord 39 Marion Leboyer 40, 41 Ann Le Couteur 42, 43 Alexander Kolevzon 2, 3, 4, 44 Patricia Jiménez González 45 Suma Jacob 46 Richard Holt 14 Stephen Guter 46 Jonathan Green 47 Andrew Green 13 Christopher Gillberg 48, 49 Bridget Fernandez 50, 51 Frederico Duque 36 Richard Delorme 52 Geraldine Dawson 53 Pauline Chaste 10 Cátia Café 36 Sean Brennan 9 Thomas Bourgeron 52 Patrick Bolton 54, 55 Sven Bölte 21 Raphael Bernier 56 Gillian Baird 57 Anthony Bailey 58, 59 Evdokia Anagnostou 60 Joana Almeida 36 Ellen Wijsman 61, 62 Veronica Vieland 63 Astrid Vicente 15, 17 Gerard Schellenberg 22, 64 Margaret Pericak-Vance 20 Andrew Paterson 8 Jeremy Parr 65, 66 Guiomar Oliveira 36, 37 John Nurnberger 67 Anthony Monaco 14 Elena Maestrini 27 Sabine Klauck 68 Hakon Hakonarson 69, 70 Jonathan Haines 24, 25 Daniel Geschwind 18 Christine Freitag 21 Susan Folstein 20, 71, 72 Sean Ennis 13 Hilary Coon 73 Agatino Battaglia 74 Peter Szatmari 12 James Sutcliffe 24, 25 Joachim Hallmayer 75 Michael Gill 9 Edwin Cook 46, 76 Joseph Buxbaum 1, 2, 3, 4, 5, 77 Bernie Devlin 10 Louise Gallagher 9 Catalina Betancur 7, * Stephen Scherer 8, 16, *
* Corresponding author
Abstract : Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Document type :
Journal articles
Complete list of metadatas

Cited literature [64 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00986225
Contributor : Catalina Betancur <>
Submitted on : Thursday, May 1, 2014 - 8:51:48 PM
Last modification on : Wednesday, September 16, 2020 - 4:32:21 PM
Long-term archiving on: : Monday, April 10, 2017 - 6:07:22 PM

Files

Pinto_AGP_CNV_AJHG_2014.pdf
Explicit agreement for this submission

  •  mmc1.pdf Explicit agreement for this submission

Identifiers

Citation

Dalila Pinto, Elsa Delaby, Daniele Merico, Mafalda Barbosa, Alison Merikangas, et al.. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.. American Journal of Human Genetics, Elsevier (Cell Press), 2014, 94 (5), pp.677-694. ⟨10.1016/j.ajhg.2014.03.018⟩. ⟨inserm-00986225⟩

Share

Metrics

Record views

14848

Files downloads

2943