Unveiling Hidden Genetic Architectures: Molecular Diagnostic Yield of Whole Exome Sequencing in 50 Children With Autism Spectrum Disorder Negative for Copy Number Variations.

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions with complex genetic etiologies. Recent advances in whole exome sequencing (WES) have enabled comprehensive detection of clinically relevant variants, particularly single-nucleotide variations (SNVs) and InDels, in ASD genetic diagnostics. Here, we performed WES on 50 Chinese children with ASD who tested negative for copy number variants (CNVs). The analysis achieved a diagnostic yield of 10% (5/50 cases). All SNVs and InDels were loss-of-function (LOF) and were slightly more frequent among females (male vs. female: 9.3% vs. 14.3%). A total of five causative genes ( and ) were identified in this study. Variants in ASD-associated genes ( and ) and genes linked to other neurodevelopmental disorders ( and ) were also detected. Despite the small sample size, our findings contribute partially to the dataset on the phenotype and genetic etiology of ASD and underscore WES as a critical tool for elucidating genetic etiologies in CNV-negative ASD cohorts.