Analysis of genes involved in neurotransmission, formation and synaptic maintenance in individuals with autistic spectrum disorders

Abstract

Autism Spectrum Disorders Diseases including Autism, Pervasive Developmental Disorder Not Otherwise Specified and Asperger Syndrome. The etiology is much debated due to its complexity and variation. These are disorders that are manifested in the first three years of life, characterized by ritualistic behavior, absent speech or poorly developed, and serious problems of social relationships and mental retardation in most cases. According to data from global epidemiology, these diseases affect approximately 1:150 individuals. In Brazil, prevalence based on this and the last census in the country, it is estimated around four millions of affected under 20 years old, emphasizing the importance of studies in this area. Can be observed association with other genetic diseases or environmental. The individuals with these diseases have been described changes in all chromosomes and genes proposed as candidates of being involved with the pathogenesis. There are several candidate genes or genomic regions that have mutations and copy number variations (CNVs), which have expression in the central nervous system. Among them are genes including UBE3A, GRM8, DLGAP2, NLGN3, NRXN1, NLGN4X, PIK3CB, PIP5K3, SHANK2 and PTEN involved in neurotransmission, synaptic formation and maintenance. This project aims to investigate these genes by the methodology of MLPA (Multiplex Ligation-dependent Probe Amplification) in individuals with autistic spectrum disorders. At least 300 individuals will be evaluated for the presence of CNVs in selected genes above. In case of change detection, it will be studied a control group with the same number of individuals and in the parents. This study may contribute to clarifying the etiology of these diseases. (AU)