Mutation Screening of the γ-Aminobutyric Acid Type-A Receptor Subunit γ2 Gene in Korean Patients with Childhood Absence Epilepsy

Abstract

Background and PurposeSince the γ-aminobutyric acid type-A receptor subunit γ2 gene (GABRG2) mutation was discovered in an Australian family with childhood absence epilepsy (CAE) and febrile convulsions, a few screening studies for the GABRG2 mutation have been conducted in sporadic individuals with CAE from other ethnic groups. The aim of this study was to determine whether or not the previously reported genetic mutations and single-nucleotide polymorphisms (SNPs) of GABRG2 can be reproduced in sporadic Korean individuals with CAE, compared to healthy Korean individuals.MethodsThirty-five children with CAE in Chonnam National University Hospital and healthy controls (n=207) were enrolled, and the medical records of patients with CAE were reviewed. CAE was diagnosed according to the Classification and Terminology of the International League Against Epilepsy. All nine exons of GABRG2 were directly sequenced. In addition, the two SNPs found in our CAE patients were analyzed: C315T in exon 3 (E3) and C588T in exon 5 (E5). The frequencies of the two SNPs in the CAE patients were compared with data from healthy controls (for E3 and E5) and from previously reported Korean population data (only for E3).ResultsNo mutation of GABRG2 was found in our CAE patients. In addition, the allele and genotype frequencies of the two polymorphisms did not differ significantly between CAE patients, healthy controls, and the Korean general population (p>0.05).ConclusionsOur study of sporadic Korean individuals with CAE found no evidence that GABRG2 contributes to the genetic basis of CAE.

Analysis of GABRG2 C588T polymorphism in genetic epilepsy and evaluation of GABRG2 in drug treatment

“… 16 , 17 , 18 , 19 C588T, located in the GABRG2 gene encoding the γ2 subunit, has previously been shown to cause genetic generalized epilepsy (GGE) risk and response to AEDs 20 , 21 , 22 ; however, other results were found to have conflicting results. 23 , 24 , 25 , 26 …”

“…[16][17][18][19] C588T, located in the GABRG2 gene encoding the γ2 subunit, has previously been shown to cause genetic generalized epilepsy (GGE) risk and response to AEDs [20][21][22] ; however, other results were found to have conflicting results. [23][24][25][26] Here, we aimed to explore whether the GABRG2 C588T polymorphism predicts susceptibility to GGE and to evaluate the role of GABRG2 in epilepsy treatment. To this end, we performed meta-analysis, functional characterization of the C588T polymorphism, protein-protein interaction (PPI) analysis, and drug-gene interaction analysis to determine the specific association.…”

“…The γ2 subunit was reported to change the kinetics of GABA A related to channels and to the synaptic and postsynaptic clustering and maintenance 16–19 . C588T, located in the GABRG2 gene encoding the γ2 subunit, has previously been shown to cause genetic generalized epilepsy (GGE) risk and response to AEDs 20–22 ; however, other results were found to have conflicting results 23–26 …”

The genetic variant “C588T” of GABARG2 is linked to childhood idiopathic generalized epilepsy and resistance to antiepileptic drugs

“…Mutations and genetic variations of GABA-A (Gamma-Aminobutyric acid type A) receptors have been associated with epilepsy. However, only limited types of epilepsy result from such mutations, which are not necessarily the direct cause of epilepsy, but the list of GABA-A receptor mutations associated with epilepsy is expected to grow [4]. The single nucleotide polymorphism in GABA-A receptors' encoding genes provides a new way to identify gene-associated epilepsy [5].…”