Abstract

Autism is a complex neurodevelopmental disorder characterized by im pair ment of so cial in ter ac tion, lan guage, com mu ni ca tion, and stereotyped, repetitive beha ior. Genetic predisposition to Au tism has been demonstrated in fam i lies and twin stud ies. There is evidence (link age and ge netic as so ci a tion, bio chem i cal, neuropathological, func tional and cytogenetic) that the gamma-amino-bu tyric acid re cep tor beta 3 sub unit gene (GABRB3) at 15q11-q13 is a sus cep ti bil ity can di date gene for Au tism. The aim of this exploratory study was to iden tify new vari ants of this gene. We per formed the mo lec u lar anal y sis (SSCP/Se quenc ing) of 10 exons and its intronic flanking regions of GABRB3, us ing a can di date gene screen ing ap proach in 18 idiopathic autistic patients. We did not find non-syn on y mous mu ta tions at the encoding regions, but we iden ti fied four SNP (Sin gle Nucleotide Polymor hism). The first one, represented a silent mutation p.P25P in exon 1a and was found in 33.33% of the pa tients. The sec ond one: IVS3+13C > T (5b far from the intron 5’ consensus sequence), was found in 44.44% of the pa tients, while it was also iden ti fied in 16.67% of the con trols. Si mul ta neously, 33.33% of the pa tients had both variants, and al though, 16.67% of the con trols also had the same combination of variants, 66.66% of the pa tients with those al leles had a fa mil iar his tory of Au tism. The third and fourth SNP: IVS5+40T > G and IVS-70A > G were iden ti fied in two dif fer ent pa tients. None of the last three SNPs have been re ported at the SNP da ta base (dbSNP). The prox im ity of SNP: IVS3+13C > T with the consensus and in ter action sequence with U1 nucleoriboprotein, could dis turb the normal splicing of mRNA. This is in agree ment with the evidence of lower lev els of GABA-A re cep tors in autistic brains; so, it could be a com mon vari ant, that by it self could not cause a phenotypic ef fect, but joined to other vari ants with the same gene, in different related genes or with epigenetic changes, could ex plain the au tis tic phenotype and its heterogeneity.