Complex Autism Spectrum Disorder in a Patient with a Novel De Novo Heterozygous Variant

Autism spectrum disorder (ASD) comprises a group of complex neurodevelopmental features seen in many different forms due to variable causes. Highly impactful ASD-susceptibility genes are involved in pathways associated with brain development, chromatin remodeling, and transcription regulation. In this study, we investigate a proband with complex ASD. Whole genome sequencing revealed a novel de novo missense mutation of a highly conserved amino acid residue (NP_001289981.1:p.His516Gln; chr2:1917275; hg38) in the neural transcription factor gene. In combination with in silico analysis on gene effect and pathogenicity, we described the proband's phenotype and made comparisons with previously reported cases to explore the spectrum of clinical features in single nucleotide variant (SNV) cases. The phenotype-genotype correlation showed a high degree of clinical similarity with previously reported cases of missense variants in indicating as the causal gene for the observed phenotype in our proband. The variant was also predicted to be damaging according to multiple in silico pathogenicity predicting tools. This study expands the clinical description of SNVs on the gene and provides insight into its contribution to ASD.