Department of Medical Genetics, University of British Columbia (UBC), Vancouver, BC V6H 3N1, Canada.
BC Children's Hospital Research Institute, Vancouver, BC V6H 3N1, Canada.
Genes (Basel). 2023 Nov 24;14(12):2122. doi: 10.3390/genes14122122.
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.
自闭症谱系障碍（ASD）是一组由于多种原因导致的不同表现形式的复杂神经发育特征。高度影响 ASD 易感性的基因参与与大脑发育、染色质重塑和转录调控相关的途径。在这项研究中，我们研究了一个具有复杂 ASD 的先证者。全基因组测序揭示了一个新的神经转录因子基因中的高度保守氨基酸残基（NP_001289981.1:p.His516Gln；chr2:1917275；hg38）的从头错义突变。结合对基因效应和致病性的计算机分析，我们描述了先证者的表型，并与以前报道的病例进行了比较，以探索单核苷酸变异（SNV）病例的临床特征谱。表型-基因型相关性显示出与以前报道的错义变异病例高度相似，表明 是我们先证者观察到表型的致病基因。该变体也被多个计算机预测致病性工具预测为有害。这项研究扩展了 基因上 SNV 的临床描述，并为其对 ASD 的贡献提供了深入了解。
