Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay

• Published in: Scientific reports 2024-11, Vol.14 (1), p.27590-11, Article 27590
• Main Authors: Li, Chengyan, Wang, You, Zeng, Cizheng, Huang, Binglong, Chen, Yinhui, Xue, Chupeng, Liu, Ling, Rong, Shiwen, Lin, Yongwen
• Format: Article
• Language: English
• Subjects: 631/208/2489; 692/308/3187; Adolescent; Autosomal dominant inheritance; Child; Child development; Child, Preschool; Children; Copy number; De novo variant; Developmental delay; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; DNA Copy Number Variations; Epilepsy; Exome Sequencing; Female; Genetic analysis; Genetic Predisposition to Disease; Genetic screening; Humanities and Social Sciences; Humans; Infant; Intellectual disabilities; Intellectual disability; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Male; multidisciplinary; Phenotypes; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Trio-whole exome sequencing; Whole genome sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-79431-x

Understanding the genetic basis of developmental delay (DD) and intellectual disability (ID) remains a considerable clinical challenge. This study evaluated the clinical application of trio whole exome sequencing (WES) in children diagnosed with DD/ID. The study comprised 173 children with unexplained DD/ID. The participants underwent trio-WES and their demographic, clinical, and genetic characteristics were evaluated. Based on their clinical features, the participants were classified into two groups for further analysis: a syndromic DD/ID group and a non-syndromic DD/ID group. The genetic diagnostic yield of the 173 children diagnosed with DD/ID was 49.7% (86/173). This included 58 pathogenic or likely pathogenic single nucleotide variants (SNVs) in 41 genes identified across 54 individuals (31.2%) through trio-WES. Among these, 22 SNVs had not been previously reported. Additionally, 30 copy number variations (CNVs) were detected in 36 individuals (20.8%). The diagnostic yield in the syndromic DD/ID group was higher than that in the non-syndromic DD/ID group (57.8% vs. 47.2%, P