Analysis of epigenetic mutation of AGTR2 gene responsible for Autism across three generation: An exploratory study

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with multifactorial unknown etiology that involves epigenetic influences. The epigenetic refers to the impact of environmental conditions on the nucleotide sequence. This exploratory study investigated the role of mutations in the AGTR2 gene, which encodes angiotensin II receptor type 2, in ASD pathogenesis. Six children with ASD participated in this study and their base pair nucleotide sequence was compared with the maternal relatives across three familial generations. Saliva samples were collected using swabbing technique, as the source for DNA extraction. Sanger sequencing was used to identify genetic mutations, especially the frameshift and point mutations in base pair nucleotide sequence of AGTR2 across three generations. Results revealed that the recurrent frameshift mutations in ASD affected individuals and their close relatives at 1-77 base pair length, suggesting potential heritable transmission. Point mutations were also observed although, their locations varied between individuals, indicating a possible contribution of de novo mutations. Consistently high adenine-thymine (A=T) content was found across all samples, suggesting genomic instability, which may act as a hotspot locus of mutation. Epigenetic mechanisms, such as DNA methylation and DNA Acetylation influenced by stressful environmental exposures were considered as the prime factor for the intergenerational inheritance of ASD susceptibility. These findings support the hypothesis that both inherited and environmental factors contribute to ASD risk, with AGTR2 emerging as a significant candidate gene for understanding complex etiology of ASD and supports the potential for AGTR2 related biomarkers in diagnosis and early intervention strategies.