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Neuron. 2013 Jan 23;77(2):259-73. doi: 10.1016/j.neuron.2012.11.002.

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

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  • 1Division of Genetics, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA. timothy.yu@childrens.harvard.edu

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

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PMID:
23352163
[PubMed - indexed for MEDLINE]
PMCID:
PMC3694430
Free PMC Article

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