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

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 (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 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.