MOLECULAR GENETIC STUDY OF AUTISM SPECTRUM DISORDER IN KHYBER PAKHTUNKHWA, PAKISTAN

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component in which rare variants contribute significantly to risk. Around 1-3% of world population are affected, and the ratio were higher in developing as compared to developed countries due to unawareness, health problems, poverty, and socio-economic problems. Out of six families, only one family was shortlisted and was recruited from Nowshera, Khyber Pakhtunkhwa province of Pakistan. Whole Exome Sequencing (WES) was performed and identified variant in shortlisted ASD family. WES Identify the possible causative gene RAS Activating protein Like 2 (RASAL2) gene. Furthermore, Sanger sequencing was performed for the confirmation of variant identified in the RASAL2 gene. After genetic analysis, clinical features were compared and to be found relative as studied in the literature. Pathogenicity of this mutation was evaluated using algorithmic mutation prediction tool. WES revealed a reported missense mutation in RASAL2 gen present on chromosome 1 in the exon 5 at c.638G>C which ultimately altered the amino acid serine to threonine at position 213. Moreover, mutation in the genes lead to disrupt the protein structure which involves in regulation of upstream and downstream pathway. In conclusion, WES was used to identify the genetic alteration in family with ASD. Mutation in RASAL2 were uncovered and clinical features of cross checking uncovered that family had ASD.