Genetic variants identification through whole-genome sequencing based on dried blood spots in 92 Chinese children with Autism

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorder with high heterogeneity. We hence to investigate the genetic etiology of ASD and the potential of whole-genome sequencing (WGS) from dried blood spots for the presymptomatic risk assessment. Total 92 individuals diagnosed with ASD were recruited to identify the genetic etiologies of ASD using WGS of newborn dried blood spots. Variants were verified with a minigene splicing assay and the construction of three-dimensional protein models. Overall, a positive molecular diagnosis was obtained for 10 cases, a rate of 10.87%. Among the 10 cases, five cases (50.0%, 5/10) were identified with likely pathogenic exon-level CNVs, two cases (20.0%, 2/10) were identified with pathogenic large CNVs, one case (10%, 1/10) was identified with the chromosomal translocation t(8;9)(q13.3;q21.13), and 2 cases (20.0%, 2/10) were identified with likely pathogenic SNVs/Indels. Total 245 variants of 173 genes were classified as “VUS”. Further functional analysis showed that one splicing variant were predicted to generate a truncated protein. Our study demonstrated the utility of WGS derived from dried blood spots for identifying ASD-associated risk genes and variants. The introduction of ASD to the newborn genetic screening should be considered, which may facilitate presymptomatic risk identification and enable earlier, more personalized interventions for high-risk infants.