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Hum Genet 2002 Aug 01;1112:154-60. doi: 10.1007/s00439-002-0766-7.
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Functional characterization of the new human GABA(A) receptor mutation beta3(R192H).

Buhr A , Bianchi MT , Baur R , Courtet P , Pignay V , Boulenger JP , Gallati S , Hinkle DJ , Macdonald RL , Sigel E .

We screened 124 individuals for single nucleotide polymorphisms of the alpha1, beta3 and gamma2 genes of the GABA(A) receptor in the regions corresponding to the ligand-binding domains on the protein level. In a patient with chronic insomnia, a missense mutation was found in the gene of the beta3 subunit. This mutation results in the substitution of the amino acid residue arginine for histidine in position 192 (beta3(R192H)). The patient was found to be heterozygous for this mutation. Functional analysis of human alpha1beta3(R192H)gamma2S GABA(A) receptors using ultra fast perfusion techniques revealed a slower rate of the fast phase of desensitization compared with alpha1beta3gamma2S GABA(A) receptors. Additionally, current deactivation [a major determinant of inhibitory postsynaptic current (IPSC) duration] was faster in the mutated receptors. This raises the possibility of decreased GABAergic inhibition contributing to insomnia, as some members of the patient's family also suffer from insomnia. The mutation beta3(R192H) might, therefore, be linked to this condition. The intron/exon boundaries of the alpha1 subunit gene were also established and three additional variants were found in the alpha1 and beta3 genes.

PubMed ID: 12189488
Article link: Hum Genet

Species referenced: Xenopus laevis
Genes referenced: gabra1 gabrb3
GO keywords: regulation of GABA-A receptor activity