title: [Molecular analysis of the GABRB3 gene in autistic patients: an exploratory study].
abstract: Autism is a complex neurodevelopmental disorder characterized by impairment of social interaction, language, communication, and stereotyped, repetitive behavior. Genetic predisposition to Autism has been demonstrated in families and twin studies. There is evidence (linkage and genetic association, biochemical, neuropathological, functional and cytogenetic) that the gamma-amino-butyric acid receptor beta 3 subunit gene (GABRB3) at 15q11-q13 is a susceptibility candidate gene for Autism. The aim of this exploratory study was to identify new variants of this gene. We performed the molecular analysis (SSCP/Sequencing) of 10 exons and its intronic flanking regions of GABRB3, using a candidate gene screening approach in 18 idiopathic autistic patients. We did not find non-synonymous mutations at the encoding regions, but we identified four SNP (Single Nucleotide Polymorphism). The first one, represented a silent mutation p.P25P in exon la and was found in 33.33% of the patients. The second one: IVS3 + 13C > T (5b far from the intron 5' consensus sequence), was found in 44.44% of the patients, while it was also identified in 16.67% of the controls. Simultaneously, 33.33% of the patients had both variants, and although, 16.67% of the controls also had the same combination of variants, 66.66% of the patients with those alleles had a familiar history of Autism. The third and fourth SNP: IVS5 + 40T > G and IVS-70A > G were identified in two different patients. None of the last three SNPs have been reported at the SNP database (dbSNP). The proximity of SNP: IVS3 + 13C > T with the consensus and interaction sequence with U1 nucleoriboprotein, could disturb the normal splicing of mRNA. This is in agreement with the evidence of lower levels of GABA-A receptors in autistic brains; so, it could be a common variant, that by itself could not cause a phenotypic effect, but joined to other variants with the same gene, in different related genes or with epigenetic changes, could explain the autistic phenotype and its heterogeneity.
authors.affiliation: Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Solís-Añez
authors.forename: Wilmer
authors.initials: W
authors.lastname: Delgado-Luengo
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Borjas-Fuentes
authors.forename: William
authors.initials: W
authors.lastname: Zabala
authors.forename: Nailet
authors.initials: N
authors.lastname: Arráiz
authors.forename: Lennie
authors.initials: L
authors.lastname: Pineda
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Portillo
authors.forename: Sandra
authors.initials: S
authors.lastname: González-Ferrer
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Chacín
authors.forename: Joaquín
authors.initials: J
authors.lastname: Peña
authors.forename: Cecilia
authors.initials: C
authors.lastname: Montiel
authors.forename: Alisandra
authors.initials: A
authors.lastname: Morales
authors.forename: Alicia
authors.initials: A
authors.lastname: Rojas de Atencio
authors.forename: Jenny
authors.initials: J
authors.lastname: Cañizales
authors.forename: Richard
authors.initials: R
authors.lastname: González
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Miranda
authors.forename: Nivia
authors.initials: N
authors.lastname: Abreu
authors.forename: Juana
authors.initials: J
authors.lastname: Delgado
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011963:Receptors, GABA-A / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C546273:GABRB3 protein, human; D011963:Receptors, GABA-A