De novo genic mutations among a Chinese autism spectrum disorder cohort

Tianyun Wang, Hui Guo, Bo Xiong, Holly Stessman, Huidan Wu, Bradley P. Coe, Tychele N. Turner, Yanling Liu, Wenjing Zhao, Kendra Hoekzema, Laura Vives, Lu Xia, Meina Tang, Jianjun Ou, Biyuan Chen, Yidong Shen, Guanglei Xun, Min Long, Janice Lin, Zev N. Kronenberg & 9 others Yu Peng, Ting Bai, Honghui Li, Xiaoyan Ke, Zhengmao Hu, Jingping Zhao, Xiaobing Zou, Kun Xia, Evan E. Eichler

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Abstract

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.

Original languageEnglish (US)
Article number13316
JournalNature Communications
Volume7
DOIs
StatePublished - Nov 8 2016
Externally publishedYes

Fingerprint

mutations
genes
Genes
disorders
Mutation
Exome
Autistic Disorder
Autism Spectrum Disorder
Recurrence

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

De novo genic mutations among a Chinese autism spectrum disorder cohort. / Wang, Tianyun; Guo, Hui; Xiong, Bo; Stessman, Holly; Wu, Huidan; Coe, Bradley P.; Turner, Tychele N.; Liu, Yanling; Zhao, Wenjing; Hoekzema, Kendra; Vives, Laura; Xia, Lu; Tang, Meina; Ou, Jianjun; Chen, Biyuan; Shen, Yidong; Xun, Guanglei; Long, Min; Lin, Janice; Kronenberg, Zev N.; Peng, Yu; Bai, Ting; Li, Honghui; Ke, Xiaoyan; Hu, Zhengmao; Zhao, Jingping; Zou, Xiaobing; Xia, Kun; Eichler, Evan E.

In: Nature Communications, Vol. 7, 13316, 08.11.2016.

Research output: Contribution to journalArticle

Wang, T, Guo, H, Xiong, B, Stessman, H, Wu, H, Coe, BP, Turner, TN, Liu, Y, Zhao, W, Hoekzema, K, Vives, L, Xia, L, Tang, M, Ou, J, Chen, B, Shen, Y, Xun, G, Long, M, Lin, J, Kronenberg, ZN, Peng, Y, Bai, T, Li, H, Ke, X, Hu, Z, Zhao, J, Zou, X, Xia, K & Eichler, EE 2016, 'De novo genic mutations among a Chinese autism spectrum disorder cohort', Nature Communications, vol. 7, 13316. https://doi.org/10.1038/ncomms13316
Wang, Tianyun ; Guo, Hui ; Xiong, Bo ; Stessman, Holly ; Wu, Huidan ; Coe, Bradley P. ; Turner, Tychele N. ; Liu, Yanling ; Zhao, Wenjing ; Hoekzema, Kendra ; Vives, Laura ; Xia, Lu ; Tang, Meina ; Ou, Jianjun ; Chen, Biyuan ; Shen, Yidong ; Xun, Guanglei ; Long, Min ; Lin, Janice ; Kronenberg, Zev N. ; Peng, Yu ; Bai, Ting ; Li, Honghui ; Ke, Xiaoyan ; Hu, Zhengmao ; Zhao, Jingping ; Zou, Xiaobing ; Xia, Kun ; Eichler, Evan E. / De novo genic mutations among a Chinese autism spectrum disorder cohort. In: Nature Communications. 2016 ; Vol. 7.
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AU - Guo, Hui

AU - Xiong, Bo

AU - Stessman, Holly

AU - Wu, Huidan

AU - Coe, Bradley P.

AU - Turner, Tychele N.

AU - Liu, Yanling

AU - Zhao, Wenjing

AU - Hoekzema, Kendra

AU - Vives, Laura

AU - Xia, Lu

AU - Tang, Meina

AU - Ou, Jianjun

AU - Chen, Biyuan

AU - Shen, Yidong

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AU - Long, Min

AU - Lin, Janice

AU - Kronenberg, Zev N.

AU - Peng, Yu

AU - Bai, Ting

AU - Li, Honghui

AU - Ke, Xiaoyan

AU - Hu, Zhengmao

AU - Zhao, Jingping

AU - Zou, Xiaobing

AU - Xia, Kun

AU - Eichler, Evan E.

PY - 2016/11/8

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N2 - 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.

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