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Cited by 71Genomic variations and chromosomal abnormalitiesAutism Spectrum Disorder ResearchGenetics and Neurodevelopmental Disorders

Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort

Open access
Guo, Hui, Peng, Yu, Hu, Zhengmao, Li, Ying, Xun, Guanglei, Ou, Jianjun, Sun, Liangdan, Xiong, Zhimin +15 more·2017·Scientific Reports
DOI 10.1038/srep44155PMC PMC5345089
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Abstract

Autism spectrum disorder (ASD) describes a group of neurodevelopmental disorders with high heritability, although the underlying genetic determinants of ASDs remain largely unknown. Large-scale whole-genome studies of copy number variation in Han Chinese samples are still lacking. We performed a genome-wide copy number variation analysis of 343 ASD trios, 203 patients with sporadic cases and 988 controls in a Chinese population using Illumina genotyping platforms to identify CNVs and related genes that may contribute to ASD risk. We identified 32 rare CNVs larger than 1 Mb in 31 patients. ASD patients were found to carry a higher global burden of rare, large CNVs than controls. Recurrent de novo or case-private CNVs were found at 15q11-13, Xp22.3, 15q13.1–13.2, 3p26.3 and 2p12. The de novo 15q11–13 duplication was more prevalent in this Chinese population than in those with European ancestry. Several genes, including GRAMD2 and STAM, were implicated as novel ASD risk genes when integrating whole-genome CNVs and whole-exome sequencing data. We also identified several CNVs that include known ASD genes (SHANK3, CDH10, CSMD1) or genes involved in nervous system development (NYAP2, ST6GAL2, GRM6). Besides, our study also implicated Contactins-NYAPs-WAVE1 pathway in ASD pathogenesis. Our findings identify ASD-related CNVs in a Chinese population and implicate novel ASD risk genes and related pathway for further study.

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  • Two de novo heterozygous missense mutations in ABI2, p.Arg373Cys and p.Glu202Lys, were identified in two ASD probands from two independent simplex quad families through exome sequencing data from the Simons Simplex Collection.

    “Two de novo heterozygous missense mutations, ABI2-p.Arg373Cys and p.Glu202Lys, were identified in two ASD probands from two independent simplex quad families through exome sequencing data retrieved from the Simons Simplex Collection (SSC)127 (Table 2w).”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [127]

    The Discussion (page unavailable) reports two de novo ABI2 missense mutations in two ASD probands from simplex quad families, identified by analyzing SSC and ASC whole-exome data. Our copy does not name the variants p.Arg373Cys and p.Glu202Lys or specify that they were heterozygous, so those details cannot be verified from it. (LLM, conf=0.84)

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  • Two de novo truncating mutations in NCKAP1 (p.Gly175TrpfsTer14 and p.Glu1088Ter) were identified in two ASD probands from two unrelated simplex quad families.

    “In the Simons Simplex Collection (SSC), two de novo truncating mutations in NCKAP1-p.Gly175TrpfsTer14 and p.Glu1088Ter- were identified in two ASD probands from two unrelated simplex quad families127.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [127]

    The Discussion (page unavailable) reports recurrent de novo likely gene-disruptive NCKAP1 mutations in ASD patients. It does not give the two variant names or establish that the NCKAP1 mutations occurred in probands from two unrelated SSC simplex quad families; the nearby statement about two such probands concerns ABI2 mutations instead. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 32

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Authors
Guo, H., Peng, Y., Hu, Z., Li, Y., Xun, G., Ou, J., Sun, L., Xiong, Z., Liu, Y., Wang, T., Chen, J., Xia, L., Bai, T., Shen, Y., Tian, Q., Hu, Y., Shen, L., Zhao, R., Zhang, X., Zhang, F., Zhao, J., Zou, X., & Xia, K.
Affiliations
  • Central South University (CN)
  • Shandong Mental Health Center (CN)
  • Third Affiliated Hospital of Sun Yat-sen University (CN)
Corresponding author
  • Zou, Xiaobing
  • Xia, Kun
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-03-10
Volume
7
Issue
1
Pages
44155-44155
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep44155
PMC
PMC5345089
OpenAlex
W2592065003
Cited by
71
References
11
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 13 · 2021: 10 · 2020: 5 · 2019: 13 · 2018: 10 · 2017: 1
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31671114, 81525007, 31400919, 81301172, 31301023, 81330027)
  • Central South University (2016CX038, 81525007)
  • China Postdoctoral Science Foundation
  • Xiangya Hospital, Central South University
  • Innovation-Driven Project of Central South University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
autism spectrum disorder, copy number variation, de novo CNVs, Xp22.3, ASD risk genes, STAM, SHANK3, CSMD1, mGluR6, Han Chinese, neurodevelopmental disorders
MeSH terms
Autism Spectrum Disorder, Adult, Child, Child, Preschool, China, Chromosomes, Human, Female, Humans, Male, Gene Dosage, Asian People, Genome-Wide Association Study, Exome

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