De novo genic mutations among a Chinese autism spectrum disorder cohort

Tianyun Wang; Hui Guo; Bo Xiong; Holly A.F. 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; Yu Peng; Ting Bai; Honghui Li; Xiaoyan Ke; Zhengmao Hu; Jingping Zhao; Xiaobing Zou; Kun Xia; Evan E. Eichler

doi:10.1038/ncomms13316

De novo genic mutations among a Chinese autism spectrum disorder cohort

Tianyun Wang, Hui Guo, Bo Xiong, Holly A.F. 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. KronenbergYu 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 language	English
Article number	13316
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13316
State	Published - Nov 8 2016

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Wang, T., Guo, H., Xiong, B., Stessman, H. A. F., Wu, H., Coe, B. P., Turner, T. N., Liu, Y., Zhao, W., Hoekzema, K., Vives, L., Xia, L., Tang, M., Ou, J., Chen, B., Shen, Y., Xun, G., Long, M., Lin, J., ... Eichler, E. E. (2016). De novo genic mutations among a Chinese autism spectrum disorder cohort. Nature communications, 7, Article 13316. https://doi.org/10.1038/ncomms13316

@article{1babc62e7639439bae79ddfaca14b728,

title = "De novo genic mutations among a Chinese autism spectrum disorder cohort",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = nov,

day = "8",

doi = "10.1038/ncomms13316",

language = "English",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

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Wang, T, Guo, H, Xiong, B, Stessman, HAF, 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

TY - JOUR

T1 - De novo genic mutations among a Chinese autism spectrum disorder cohort

AU - Wang, Tianyun

AU - Guo, Hui

AU - Xiong, Bo

AU - Stessman, Holly A.F.

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

AU - Xun, Guanglei

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

Y1 - 2016/11/8

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84994761167&partnerID=8YFLogxK

U2 - 10.1038/ncomms13316

DO - 10.1038/ncomms13316

M3 - Article

C2 - 27824329

AN - SCOPUS:84994761167

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 13316

ER -

De novo genic mutations among a Chinese autism spectrum disorder cohort

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