Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations

Hum Mutat. 2019 Jun;40(6):801-815. doi: 10.1002/humu.23724. Epub 2019 Apr 29.


Autism spectrum disorder (ASD) is a childhood neuropsychiatric disorder with a complex genetic architecture. The diagnostic potential of a targeted panel of ASD genes has only been evaluated in small cohorts to date and is especially understudied in the Chinese population. Here, we designed a capture panel with 358 genes (111 syndromic and 247 nonsyndromic) for ASD and sequenced a Chinese cohort of 539 cases evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) as well as 512 controls. ASD cases were found to carry significantly more ultra-rare functional variants than controls. A subset of 78 syndromic and 54 nonsyndromic genes was the most significantly associated and should be given high priority in the future screening of ASD patients. Pathogenic and likely pathogenic variants were detected in 9.5% of cases. Variants in SHANK3 and SHANK2 were the most frequent, especially in females, and occurred in 1.2% of cases. Duplications of 15q11-13 were detected in 0.8% of cases. Variants in CNTNAP2 and MEF2C were correlated with epilepsy/tics in cases. Our findings reveal the diagnostic potential of ASD genetic panel testing and new insights regarding the variant spectrum. Genotype-phenotype correlations may facilitate the diagnosis and management of ASD.

Keywords: Chinese; autism; genetic testing; targeted resequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics*
  • Autism Spectrum Disorder / diagnosis*
  • Autism Spectrum Disorder / genetics
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Gene Regulatory Networks*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • MEF2 Transcription Factors / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Sequence Analysis, DNA / methods*
  • Young Adult


  • CNTNAP2 protein, human
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SHANK2 protein, human
  • SHANK3 protein, human