Disease relevance of GABRG2

• Although missense mutations in the GABA(A) receptor gamma2 subunits (GABRG2) gene have recently been detected in two families with typical absence seizures, no study has been carried out to clarify the relationship between atypical absence and GABA(A) receptors [1].
• We now report a K289M mutation in the GABA(A) receptor gamma2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes [2].
• OBJECTIVE: To assess the role of GABRG2 in the genetic predisposition to idiopathic absence epilepsies [3].

High impact information on GABRG2

• We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures [4].
• Using panels of chromosome-specific natural deletion hybrids, we have further localized the gamma 1 gene (GABRG1) to 4p14-q21.1 and the gamma 2 gene (GABRG2) to 5q31.1-q33 [5].
• RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region [6].
• HeLa cell nuclear extract contained a protein that specifically binds to CAE1 and CAE2 and recognized by anti-ZNF143 antibody [7].
• A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions [3].

Chemical compound and disease context of GABRG2

• Mutations in the gene encoding the gamma2 subunit of the gamma-aminobutyric acid type A receptor (GABRG2) have been reported to cause childhood absence epilepsy (CAE), febrile seizures (FS), and generalized epilepsy with FS plus (GEFS+) [8].

Biological context of GABRG2

• These results reveal the clustering of GABRA6, GABRA1, and the GABAA receptor gamma 2-subunit gene (GABRG2) on distal chromosome 5q [9].
• By performing an association study, we used single-nucleotide polymorphisms to investigate the distribution of genotypes of GABRG2 in patients with FSs [10].
• The molecular study included analysis of polymerase chain reaction (PCR) fragments of SCN1A and SCN1B exons by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing of GABRG2 in all families [11].
• In contrast, the number of individuals with the GABRG2 (SNP211037)-C/C genotype in patients with FSs was significantly greater compared with that in healthy control subjects (p = 0.017), and the GABRG2 (SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects (p = 0.009) [10].
• Although we found no mutation in the exons of GABRG2, we did identify two single nucleotide polymorphisms (SNPs) in exon 3 and exon 5 [12].

Anatomical context of GABRG2

• Gephyrin and GABRG2 immunoreactivities in the striatum and hippocampus of the ChAc-model mice were significantly higher than those in the wild types [13].

Associations of GABRG2 with chemical compounds

• CONTEXT: Missense mutations in the GABRG2 gene, which encodes the gamma 2 subunit of central nervous gamma-aminobutyric acid (GABA)(A) receptors, have recently been described in 2 families with idiopathic epilepsy [3].
• Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder [14].

Other interactions of GABRG2

• Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with absence seizures [1].
• CONCLUSIONS: The most frequently observed phenotypes matched those reported in families with mutations of the SCN1A, SCN1B, and GABRG2 genes [11].
• A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002) [15].
• The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA beta2 (GABRB2) and gamma2 (GABRG2) genes on chromosome 5q33 [15].
• The environment and childhood asthma (ECA) study in Oslo: ECA-1 and ECA-2 [16].

Analytical, diagnostic and therapeutic context of GABRG2

• PCR was used to identify the C/T and A/G polymorphisms of the GABRG2 gene on chromosome 5q33 [10].
• Mutational screening of GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram [17].
• This finding partly replicates a recent case-control study of GABRG2 in METH use disorder, and thus indicates that GABRG2 may be one of the susceptibility genes of METH use disorder [14].

References