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

Choi, Ji Eun; Chae, Jong Hee; Kim, Ki Joong; Hwang, Yong Seung

Abstract

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.