Whole-Exome Sequencing Identifies One De Novo Variant in theFGD6Gene in a Thai Family with Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) has a strong genetic basis, although the genetics of autism is complex and it is unclear. Genetic testing such as microarray or sequencing was widely used to identify autism markers, but they are unsuccessful in several cases. The objective of this study is to identify causative variants of autism in two Thai families by using whole-exome sequencing technique. Whole-exome sequencing was performed with autism-affected children from two unrelated families. Each sample was sequenced on SOLiD 5500xl Genetic Analyzer system followed by combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were validated, and the segregation study with other family members was performed using Sanger sequencing. This study identified a possible causative variant for ASD, c.2951G>A, in the FGD6 gene. We demonstrated the potential for ASD genetic variants associated with ASD using whole-exome sequencing and a bioinformatics filtering procedure. These techniques could be useful in identifying possible causative ASD variants, especially in cases in which variants cannot be identified by other techniques.

Comparative analysis of the autism‑related variants between different autistic children in a family pedigree

“…in recent years, remarkable progress has been made towards understanding the genetic risks of autism using WES (22,23). For example, some de novo mutations were found by comparing the WeSs of sporadic cases with those of their parents (17,(24)(25)(26)(27)(28)(29). it has been suggested that these de novo mutations can increase the risk of autism but may not lead to autism.…”

“…it has been suggested that these de novo mutations can increase the risk of autism but may not lead to autism. Therefore, it is necessary to perform a WeS study based on the family pedigree of aSd patients to explore possible hereditary mutations (14)(15)(16)(17).…”

“…comprehensive analysis of the whole exome aids in the identification of disease-related coding region mutations to determine the impact of these dna mutations on the pathogenesis of a disease (12). There are a few reports on how to preliminarily screen for gene mutations of familial autism based on a large number of mutations annotated from the WeS results and how to further identify highly credible autism-related genes (13)(14)(15)(16)(17)(18). However, the screening conditions and parameters used are not consistent.…”

Pharmacogenomics and non-genetic factors affecting drug response in autism spectrum disorder in Thai and other populations: current evidence and future implications

“…Some copy number variations (CNVs) may have been associated with the increased risk of developing ASD ( Bernier et al, 2016 ; Zarrei et al, 2019 ; Bauleo et al, 2021 ; Costa et al, 2022 ). A recent whole-exome sequencing study identified one de novo causative variant (c.2951G>A) in the FGD6 gene (OMIM ID: 613520) in Thai ASD patients ( Thongnak et al, 2018 ).…”

Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample

“…Therefore, the selection of de novo missense mutations has become a problem requiring further investigation. Relevant software programs (e.g., SIFT [Sorting Intolerant From Tolerant], MutationTaster) have been used to assess the harmfulness and conservation of gene mutation sites (Thongnak et al 2018 (Li et al 2016), which prioritize the list of genes depending on the impact of mutations and assess the tolerance of genes to genetic mutations, have also been used. However, the relationship between genes and phenotypes has not been analyzed or predicted.…”