Molecular Analysis of Neuronal Cell Surface Protein gene; Neuroligin 3 in Autism Spectrum Disorder

Abstract

Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that manifests before the age of three. ASD is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic patterns of interests and behavior. More than 1 million cases per year are reported in India. It is now believed that ASD is due to complex genetic and environmental interactions. Changes in over 1,000 genes have been reported to be associated with ASD. Many of the associated genes are involved in the development and functions of the brain. The proposed candidate gene for ASD includes the Neuroligin (NLGN). It is a cell adhesion protein on the postsynaptic membrane involved in Synaptogenesis. Objective: To screen the variants in NLGN3 gene associated with Autism Spectrum Disorder. Methods: 1821 mentally ill children from the North Karnataka region of Karnataka, India were screened as per DSM-V Criteria and 108 autistic were included in the study. Genomic DNA was extracted and the candidate gene was amplified using standard PCR condition. The product was sequenced for genetic variation. Result: one 5' UTR variant, one missense variant, and four 3' UTR variants were recorded. The novel Coding sequence variant c.551 T>C transition was observed in 16 autistics (14.81%). This transition changes Valine to Alanine (p.Val184Ala). This may lead to abnormal neuronal cell surface Protein. Conclusion: This was the first study in Karnataka on genetic aspects of autism. Only one coding sequence variant was observed in 14.81% of our population. This variant may lead to potentially abnormal Neuroligin for the etiology of autism in north Karnataka.