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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.

The Duchenne/Becker Muscular Dystrophy (DMD/BMD) is an X linked recessive lethal disease. The female carrier will transmit the disease gene to half of her sons and half of her daughters; half of the daughters will be carriers, while half will be normal. Half of the sons will be normal and, on average, half will have the disease. It is of particular relevance to be able to detect carrier status among female relatives of the patients for genetic counseling and prenatal diagnosis. The method of Short Tandem Repeat (STR) sequence polymorphism analysis can determine haplotype at normal status or at risk status and, to establish genetic linkage between the mutated gene and the segregated haplotype. We have analyzed 105 members from 15 unrelated Venezuelan families with one or more siblings affected with DMD/DMB and 7 unrelated males. Of the 105, 37 were male (26 affected and 11 normal) and 68 were female. STR sequences (STR44, STR45, STR49, STR50, STR3'DYS) of the gene of the Dystrophin were amplified by polymerase chain reaction (PCR) to analyze allelic polymorphism in the families. Five of the 15 families (33%) had a deletion of one or several of the exons. Of the 68 females, 27 (39.7%) were carriers, 27 (39.7%) were non-carriers and in 14 cases (20.58%) it was not possible to reach a definitive diagnosis. The definitive diagnosis could be established in 79% of the females. This analysis also shows that the mutation occurred on the grandpaternal X chromosome in one family. Hemizygocity was detected and carrier status ascertained in the mother of other patient and in one family we were able to do prenatal diagnosis. The germinal mosaicism could not be excluded in 3 patients.