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Lookup NU author(s): Lynne Overman
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© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. Autism spectrum disorder (ASD) affects up to 1 in 59 individuals1. Genome-wide association and large-scale sequencing studies strongly implicate both common variants2–4 and rare de novo variants5–10 in ASD. Recessive mutations have also been implicated11–14 but their contribution remains less well defined. Here we demonstrate an excess of biallelic loss-of-function and damaging missense mutations in a large ASD cohort, corresponding to approximately 5% of total cases, including 10% of females, consistent with a female protective effect. We document biallelic disruption of known or emerging recessive neurodevelopmental genes (CA2,DDHD1,NSUN2,PAH,RARB,ROGDI,SLC1A1,USH2A) as well as other genes not previously implicated in ASD including FEV (FEV transcription factor, ETS family member), which encodes a key regulator of the serotonergic circuitry. Our data refine estimates of the contribution of recessive mutation to ASD and suggest new paths for illuminating previously unknown biological pathways responsible for this condition.
Author(s): Doan RN, Lim ET, De Rubeis S, Betancur C, Cutler DJ, Chiocchetti AG, Overman LM, Soucy A, Goetze S, Freitag CM, Daly MJ, Walsh CA, Buxbaum JD, Yu TW
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Print publication date: 01/07/2019
Online publication date: 17/06/2019
Acceptance date: 02/05/2019
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Nature Publishing Group
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