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Neuron DOI:10.1016/j.neuron.2012.11.002

Using whole-exome sequencing to identify inherited causes of autism.

Publication TypeJournal Article
Year of Publication2013
AuthorsYu, TW, Chahrour, MH, Coulter, ME, Jiralerspong, S, Okamura-Ikeda, K, Ataman, B, Schmitz-Abe, K, Harmin, DA, Adli, M, Malik, AN, D'Gama, AM, Lim, ET, Sanders, SJ, Mochida, GH, Partlow, JN, Sunu, CM, Felie, JM, Rodriguez, J, Nasir, RH, Ware, J, Joseph, RM, R Hill, S, Kwan, BY, Al-Saffar, M, Mukaddes, NM, Hashmi, A, Balkhy, S, Gascon, GG, Hisama, FM, LeClair, E, Poduri, A, Oner, O, Al-Saad, S, Al-Awadi, SA, Bastaki, L, Ben-Omran, T, Teebi, AS, Al-Gazali, L, Eapen, V, Stevens, CR, Rappaport, L, Gabriel, SB, Markianos, K, State, MW, Greenberg, ME, Taniguchi, H, Braverman, NE, Morrow, EM, Walsh, CA
JournalNeuron
Volume77
Issue2
Pages259-73
Date Published2013 Jan 23
ISSN1097-4199
KeywordsAdolescent, Animals, Autistic Disorder, Cells, Cultured, Child, Child, Preschool, Cohort Studies, Exome, Female, Genome-Wide Association Study, Humans, Male, Pedigree, Rats, Sequence Analysis, DNA, Young Adult
Abstract

Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole-exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, and POMGNT1). At least some of these genes show biallelic mutations in nonconsanguineous families as well. These mutations are often only partially disabling or present atypically, with patients lacking diagnostic features of the Mendelian disorders with which these genes are classically associated. Our study shows the utility of WES for identifying specific genetic conditions not clinically suspected and the importance of partial loss of gene function in ASDs.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0896-6273(12)00993-2
DOI10.1016/j.neuron.2012.11.002
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23352163?dopt=Abstract

Alternate JournalNeuron
PubMed ID23352163
PubMed Central IDPMC3694430
Grant ListR01 MH083565 / MH / NIMH NIH HHS / United States
T32 NS007473-12 / NS / NINDS NIH HHS / United States
T32 AG000222 / AG / NIA NIH HHS / United States
RC2 MH089952 / MH / NIMH NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
T32GM07753 / GM / NIGMS NIH HHS / United States
T32 NS007484-08 / NS / NINDS NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
1RC2MH089952 / MH / NIMH NIH HHS / United States
T32 MH020017 / MH / NIMH NIH HHS / United States
K23 MH080954 / MH / NIMH NIH HHS / United States
K23NS069784 / NS / NINDS NIH HHS / United States
T32 NS007473 / NS / NINDS NIH HHS / United States
1K23MH080954-01 / MH / NIMH NIH HHS / United States
R01 NS048276 / NS / NINDS NIH HHS / United States
K23 NS069784 / NS / NINDS NIH HHS / United States
T32 NS007484 / NS / NINDS NIH HHS / United States