Single Nucleotide Polymorphisms of GABRG2 in Idiopathic Generalized Epilepsies(IGEs) / 대한소아신경학회지

PURPOSE: Mutations in gamma-aminobutyric acid(GABA) A receptor gamma2 subunit gene (GABRG2) were independently identified in families of generalized epilepsy with febrile seizures plus(GEFS+) and families of absence epilepsy and febrile seizures(FSs). The present study assessed the role of GABRG2 gene in idiopathic generalized epilepsies(IGEs) of Korean population. METHODS: Twenty-three IGEs and 94 healthy control subjects were selected through a collaborative study of Catholic Child Neurology Research Group. The SNP211037 of GABRG2 were screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. Genotypes and allelic frequencies for GABRG2 gene polymorphism in three groups were compared. RESULTS: Genotypes and allelic frequencies of the gamma2 subunit of the GABA receptor gene(SNP211037) in both groups were not significantly different. The most common genotypes for GABRG2(SNP211037) gene in both groups were T/C heterozygote. The allele C and T frequencies for GABRG2(SNP211037) in the IGEs group were 45.7% and 54.3%, respectively and in healthy control group, 42.6% and 57.4%, respectively. The number of individuals with the GABRG2 (SNP211037)-C/C genotype in the IGEs group was greater compared with that in the healthy control group(21.7% versus 12.8%). The odds ratio for developing IGEs in individuals with the GABRG2 (SNP211037)-CC genotype was 1.65 compared with individuals with the GABRG2 (SNP211037)-T/T genotype, which was not significantly different. CONCLUSION: These data suggest that genomic variations of GABRG2 might not be one of the susceptibility factors for IGEs in the Korean population.

Single Nucleotide Polymorphisms of GABRG2 in Febrile Seizures and GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizures are characterized by a heterogenous phenotype segregating as an autosomal dominant trait with incomplete penetrance. Mutations in GABRG2 gene were identified in two families with generalized epilepsy and febrile seizures plus (GEFS+) and with absence epilepsy and febrile seizures(FSs). The present study assessed the role of GABRG2 gene in FSs and GEFS+ of the Korean population. METHODS: 66 FSs, 20 GEFS+ and 94 healthy control subjects were selected throughout a collaborative study of Catholic Child Neurology Research Group. The SNP211037 of GABRG2 was screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. Genotypes and allelic frequencies for GABRG2 gene polymorphism in three groups were compared. RESULTS: 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 and the GABRG2(SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects. The odds ratio for developing FSs in individuals with the GABRG2(SNP211037)-CC genotype was 5.96 compard with individuals with the GABRG2(SNP211037)-T/T genotype. In contrast, the GABRG2 (SNP211037) gene in GEFS+ and control groups was not significantly different. CONCLUSION: Theses data suggest that genomic variations of GABRG2 might be one of the susceptibility factors for FSs in the Korean population.

Mutational Analysis of GABAA Receptor gamma2 Subunit Gene, GABRG2, in Patients with Febrile Seizure or Generalized Epilepsy with Febrile Seizure Plus / 대한소아신경학회지

PURPOSE: The GABAergic system has long been implicated in epilepsy with defects in GABA neurotransmission linked to epilepsy in both experimental animal models and human syndromes. Recently, mutations in the GABA(A) receptor gamma 2 subunit (GABRG2) gene were identified in two families with generalized epilepsy with febrile seizures plus(GEFS+) and two families with childhood absence epilepsy and febrile seizures. We tested the hypothesis that genetic variations in the GABRG2 gene confer susceptibility to febrile seizure in the Korean population. METHODS: A total of 22 febrile seizure patients with or without afebrile seizures were selected. To identify unknown mutations in GABRG2 gene, a total of nine exons were amplified and screened by DHPLC method. DNA fragments showing abnormal DHPLC elution patterns were subsequently sequenced. RESULTS: Among 22 febrile seizure patients, 5 patents(23%) were familial and 7 patients were sporadic cases. And 17(77%) experienced afebrile seizures and 5 patients didn't. Seizure types of 17 febrile patients with afebrile seizure were 13 idiopathic generalized epilepsies, 1 juvenile myoclonic epilepsy, 1 childhood absence epilelsy and 2 complex partial seizures. We identified two single nucleotide polymorphisms in exon 1 and exon 3. In exon 1, C69C/T polymorphism(dsSNP:3219203) was identified in 4 patients, which had already been reported. In exon 3, C541C/T polymorphism was identified in nine patients and eight patients showed C/T hetero forms and one patient showed T/T homo mutant form. This C541C/T allelic variations were novel and identified in febrile seizure patients with afebrile seizures. But this variation didn't show significant correlations with febrile seizure patterns or family history of patients. CONCLUSION: Our study identified two exonal polymorphisms and one is novel. The GABRG2 gene seems to confer a rare rather than a frequent major susceptility effect to febrile seizure.