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

Researchers used advanced genetic testing called whole exome sequencing on 50 Chinese children with autism who had normal results on previous genetic tests. They found genetic causes for autism in 10% of these children (5 out of 50). The genetic changes were slightly more common in girls than boys. This study shows that more detailed genetic testing can sometimes find answers even when basic genetic tests come back normal.

This study examined whole exome sequencing (WES) in 50 Chinese children with autism spectrum disorder who previously tested negative for copy number variations. The research achieved a 10% diagnostic yield, identifying genetic variants in 5 cases. All identified variants were loss-of-function mutations, with slightly higher frequency in females (14.3%) compared to males (9.3%). Five causative genes were identified, along with variants in genes associated with autism and other neurodevelopmental disorders.

The findings support WES as an important diagnostic tool for identifying genetic causes in autism cases where initial genetic testing is negative.

WES should be considered for autism diagnosis when initial CNV testing is negative, with potential for 10% diagnostic yield. Results may inform genetic counseling and family planning decisions. Gender differences in diagnostic yield warrant further investigation with larger samples.

Small sample size of 50 participants limits generalizability. Study focused only on Chinese children, restricting ethnic diversity. The specific causative genes are not clearly detailed in the abstract, limiting clinical applicability of findings.

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.