The Role of Ion Channel-Related Genes in Autism Spectrum Disorder: A Study Using Next-Generation Sequencing

Abstract

The clinical heterogeneity of autism spectrum disorder (ASD) is closely associated with the diversity of genes related to ASD pathogenesis. With their low effect size, it has been hard to define the role of common variants of genes in ASD phenotype. In this study, we reviewed genetic results and clinical scores widely used for ASD diagnosis to investigate the role of genes in ASD phenotype considering their functions in molecular pathways. Genetic data from next-generation sequencing (NGS) were collected from 94 participants with ASD. We analyzed enrichment of cellular processes and gene ontology using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We compared clinical characteristics according to genetic functional characteristics. We found 266 genes containing nonsense, frame shift, missense, and splice site mutations. Results from DAVID revealed significant enrichment for “ion channel” with an enrichment score of 8.84. Moreover, ASD participants carrying mutations in ion channel-related genes showed higher total IQ (p = 0.013) and lower repetitive, restricted behavior (RRB)-related scores (p = 0.003) and mannerism subscale of social responsiveness scale scores, compared to other participants. Individuals with variants in ion channel genes showed lower RRB scores, suggesting that ion channel genes might be relatively less associated with RRB pathogenesis. These results contribute to understanding of the role of common variants in ASD and could be important in the development of precision medicine of ASD.

Nexus between genome-wide copy number variations and autism spectrum disorder in Northeast Han Chinese population

“…Interestingly, dysfunction of axon-guidance signaling is integral to the microstructural abnormalities of the brain in people with ASD [ 84 ]. Notably, the involvement of ion channel-related genes has been found in ASD etiology [ 85 ]. Mutations in ion channel genes contribute to low-to-moderate susceptibility of ASD [ 85 ].…”

“…Notably, the involvement of ion channel-related genes has been found in ASD etiology [ 85 ]. Mutations in ion channel genes contribute to low-to-moderate susceptibility of ASD [ 85 ].…”

Medical and social problems of education and adaptation in children and adolescents with autism spectrum disorders

“…При этом показано отсутствие до настоящего времени серологических маркеров, ассоциированных с РАС и отвечающих всем требованиям по чувствительности и специфичности [11]. Полагают, что клиническая гетерогенность РАС связана с разнообразием генов, обусловливающих патогенез РАС хотя возрастающую частоту встречаемости РАС считают пока мало объяснимой [12]. Увеличение встречаемости РАС нельзя связать с изменениями в детской психиатрической службе и диагностическими критериями.…”