Genetic Analysis of Children With Unexplained Developmental Delay and/or Intellectual Disability by Whole-Exome Sequencing

Jingjing Xiang; Yang Ding; Fei Yang; Ang Gao; Wei Zhang; Hui Tang; Jun Mao; Quanze He; Qin Zhang; Ting Wang

doi:10.3389/fgene.2021.738561

Genetic Analysis of Children With Unexplained Developmental Delay and/or Intellectual Disability by Whole-Exome Sequencing

Front Genet. 2021 Nov 10:12:738561. doi: 10.3389/fgene.2021.738561. eCollection 2021.

Authors

Jingjing Xiang^{1

2}, Yang Ding^{1

2}, Fei Yang^{1

2}, Ang Gao^{1

2}, Wei Zhang^{1

2}, Hui Tang^{1

2}, Jun Mao^{1

2}, Quanze He^{1

2}, Qin Zhang^{1

2}, Ting Wang^{1

2}

Affiliations

¹ Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
² Center for Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou, China.

Abstract

Background: Whole-exome sequencing (WES) has been recommended as a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders (NDDs). We aimed to identify the genetic causes of 17 children with developmental delay (DD) and/or intellectual disability (ID). Methods: WES and exome-based copy number variation (CNV) analysis were performed for 17 patients with unexplained DD/ID. Results: Single-nucleotide variant (SNV)/small insertion or deletion (Indel) analysis and exome-based CNV calling yielded an overall diagnostic rate of 58.8% (10/17), of which diagnostic SNVs/Indels accounted for 41.2% (7/17) and diagnostic CNVs accounted for 17.6% (3/17). Conclusion: Our findings expand the known mutation spectrum of genes related to DD/ID and indicate that exome-based CNV analysis could improve the diagnostic yield of patients with DD/ID.

Keywords: developmental delay; exome-based CNV analysis; intellectual disability; variants; whole-exome sequencing.