Screening of GABA(A)-receptor gene mutations in primary dystonia.

Several lines of evidence suggest that GABA-ergic neurotransmission plays a role in the pathogenesis of primary dystonia in humans. In this study, we tested the hypothesis that mutations in the GABRA1, GABRB3, and GABRG2 genes encoding the alpha1, beta3, and gamma subunits of the GABA(A) receptor are involved in familial primary dystonia. All exons and exon-intron boundaries of the above genes were amplified by PCR from genomic DNA in 28 patients who had primary dystonia and a positive family history but had no mutation in any other genes known to be involved in primary dystonia. The PCR products were analyzed by single strand conformation polymorphism followed by sequencing of variant conformers compared with normal controls (n = 54). We found no mutations in these genes. We did, however, find a new polymorphism, 559 + 80G>A in intron 5 of GABRA1, and we also confirmed several that were previously reported, including 315C>T in exon 3 and 588C>T in exon 5 of GABRG2, but there were no significant differences between controls and patients in the allele and genotype frequencies of these polymorphisms. In conclusion, mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia.