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

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