Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10

Mol Autism. 2017 Jun 26;8:31. doi: 10.1186/s13229-017-0136-x. eCollection 2017.

Abstract

Background: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD.

Methods: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature.

Results: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases.

Conclusions: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings.

Keywords: Array comparative genomic hybridization (aCGH); Autism spectrum disorder (ASD); Chinese; Copy number variations (CNVs); DPP10.

MeSH terms

  • Adolescent
  • Adult
  • Asians
  • Autism Spectrum Disorder / genetics*
  • Child
  • Child, Preschool
  • China
  • Chromosomes, Human / genetics*
  • DNA Copy Number Variations*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Oligonucleotide Array Sequence Analysis / methods*

Substances

  • DPP10 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases