Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China

Genes (Basel). 2022 Jun 2;13(6):1010. doi: 10.3390/genes13061010.


Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the SHANK3 gene has the greatest number of reportable variants, followed by gene MYT1L. Patients with MYT1L variants share common and specific clinical characteristics. We found a child with compound heterozygous SLC26A4 variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition.

Keywords: MYT1L; SLC26A4; autism spectrum disorder; genetic variants; targeted panel sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder* / diagnosis
  • Autism Spectrum Disorder* / genetics
  • China
  • DNA Copy Number Variations / genetics
  • Humans
  • Phenotype

Grants and funding

This research was funded in part by the National Natural Science Foundation of China (NSFC, No. 82171540), the Key Subject Construction Project of Shanghai Municipal Health Commission (No. shslczdzk02903) and the Young Clinical Scientist Program of Children’s Hospital of Fudan university (No. 2022LCKXJ03).