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Nat Commun. 2016 Nov 8;7:13316. doi: 10.1038/ncomms13316.

De novo genic mutations among a Chinese autism spectrum disorder cohort.

Author information

The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Children's Development Behavior Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Mental Health Center of Shandong Province, Jinan, Shandong 250014, China.
Child Healthcare Department, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi 545000, China.
Child Mental Health Research Center, Nanjing Brain Hospital Affiliated of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Collaborative Innovation Center for Genetics and Development, Shanghai 200433, China.
Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan 410013, China.
Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.


Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1.1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L. We identify novel DN LGD recurrences (GIGYF2, MYT1L, CUL3, DOCK8 and ZNF292) and DN mutations in previous ASD candidates (ARHGAP32, NCOR1, PHIP, STXBP1, CDKL5 and SHANK1). Phenotypic follow-up confirms potential subtypes and highlights how large global cohorts might be leveraged to prove the pathogenic significance of individually rare mutations.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

E.E.E. is on the scientific advisory board (SAB) of DNAnexus, Inc. and was an SAB member of Pacific Biosciences, Inc. (2009–2013) and SynapDx Corp. (2011–2013); E.E.E. is a consultant for Kunming University of Science and Technology (KUST) as part of the 1,000 China Talent Program. The other authors declare no competing financial interests.

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