Identification of genetic variants and their causal association underlying autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with a complex genetic architecture characterized by persistent deficits in social communication and social interaction along with restricted and repetitive behavior patterns, interests and activities. Over the years its prevalence has increased and affects 1% children globally. Etiology of ASD is remained unclear, but it is well recognized as a complex disorder involving interactions of several genes and environmental risk factors. Studies signify the role of whole exome sequencing in identifying rare genetic variation related to neurodevelopmental disorders and have greatly improved the chance of identifying known as well as novel responsible genes. This study aimed to identify genetic variant in a patient affected with autism spectrum disorder. MethodsA male patient of age range 0-5 years was investigated and identified according to DSM-5 criteria for autism spectrum disorder. Peripheral blood sample was collected followed by genomic DNA extraction and whole exome sequencing. The functional impact of variant, gene interaction network and pathway enrichment analysis were done using in silico tools and databases. ResultsTwo heterozygous missense variants one in SHANK2 (c.401C>G) another in CSNK2A1 (c.572G>A) were identified. Both of these variants were predicted to be deleterious by pathogenicity prediction tool. Gene interaction network and pathway enrichment analysis revealed the involvement of SHANK2 and CSNK2A1 in various biological pathways such as protein binging, synaptogenesis, chromosome condensation and cell cycle regulation. ConclusionThis study revealed a novel SHANK2 variant along with a known CSNK2A1 variant that expands the spectrum of genetic variants related to autism spectrum disorder and further enhances the understanding of the molecular mechanism underlying SHANK2 and CSNK2A1 pathophysiology.