Genetic etiology analysis of developmental delay/intellectual disability in children based on whole-exome sequencing combined with copy number variation analysis

SU Wei; XU Yanhong; LI Hong

doi:10.11852/zgetbjzz2025-0742

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Chinese Journal of Child Health Care ›› 2026, Vol. 34 ›› Issue (11) : 1183-1188. DOI: 10.11852/zgetbjzz2025-0742

Birth Defect Screening and Genetic Diagnosis

Genetic etiology analysis of developmental delay/intellectual disability in children based on whole-exome sequencing combined with copy number variation analysis

SU Wei, XU Yanhong, LI Hong

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Abstract

Objective To evaluate the diagnostic value of whole-exome sequencing (WES) combined with copy number variation (CNV) analysis in children with unexplained developmental delay or intellectual disability (DD/ID), so as to provide a reference for clinical practice. Methods A retrospective study was conducted among 109 children with unexplained DD/ID who visited the Department of Rehabilitation, Anhui Provincial Children′s Hospital, from January to December 2024. WES data were analyzed to systematically evaluate single nucleotide variants (SNV), small insertions/deletions (Indel), and CNV. Pathogenicity was comprehensively interpreted integrating family validation and clinical phenotypes. Results SNV/Indel analysis identified 18 pathogenic and 23 likely pathogenic variants, with a diagnostic yield of 37.61%. Frameshift variants were the most prevalent (36.6%), and heterozygous variants constituted the majority (90.2%). Autosomal dominant inheritance was the most common mode (48.8%). Furthermore, CNV analysis identified 10 pathogenic or 2 likely pathogenic variants involving multiple genes associated with neurodevelopment, increasing the overall diagnostic yield by 11.01%. Conclusion WES combined with CNV analysis significantly improves the molecular diagnostic yield in children with unexplained DD/ID, which provides crucial reference for genetic counseling and precision medicine.

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whole-exome sequencing / copy number variation / developmental delay / intellectual disability

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SU Wei, XU Yanhong, LI Hong. Genetic etiology analysis of developmental delay/intellectual disability in children based on whole-exome sequencing combined with copy number variation analysis[J]. Chinese Journal of Child Health Care. 2026, 34(11): 1183-1188 https://doi.org/10.11852/zgetbjzz2025-0742

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