期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13316
关键词
-
资金
- National Basic Research Program of China [2012CB517900]
- National Natural Science Foundation of China [81330027, 81525007, 31400919]
- China Postdoctoral Science Foundation [2015M570684]
- Innovation-Driven Project of Central South University [2016CX038]
- Young Talent Lifts Project of CAST
- China Scholarship Council [201406370028]
- Fundamental Research Funds for the Central Universities [2012zzts110]
- Simons Foundation Autism Research Initiative [SFARI 303241]
- NIH [R01MH101221]
- NHGRI Interdisciplinary Training in Genome Science Grant [T32HG00035]
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, similar to 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据