J Korean Child Neurol Soc.  2008 May;16(1):19-27.

Association Analysis of Voltage-gated Chloride Channel Gene CLCN2 Polymorphism with Idiopathic Generalized Epilepsy

• Choi JE
• Hwang H
• Chae JH
• Kim KJ
• Hwang YS

Abstract

PURPOSE: The channelopathies has been implicated in the pathogenesis of idiopathic generalized epilepsy(IGE). Recently, nonsense and missense mutations in a voltage-gated chloride channel gene(CLCN2) have been shown to be associated with IGE. Loss of CLCN2 function results in loss of sustained GABA inhibition, increasing the risk of uncontrolled firing leading to seizure activity. This study assessed the relevance of mutations in the CLCN2 gene in the Korean patients with IGE.
METHODS
Twenty seven patients with IGE were recruited in the Seoul National University Boramae Hospital. PCR and direct sequencing of genomic DNA were done to analyze the complete coding region of CLCN2. 99 controls were tested for two identified polymorphisms. Genotypes and allelic frequencies were compared to controls with epilepsy patients and subgroup of IGE: 10 generalized epilepsy with febrile seizure plus(GEFSP), 9 childhood absence epilepsy(CAE) and 8 other IGE patients.
RESULTS
Twelve CLCN2 polymorphisms: 3 exonic, 2 promotor and 7 intronic, were found in 22 patients(81%) and 2 polymorphisms were noble. Two polymorphisms in the exonic region with changes of amino acid, p.L15P and p.T668S and 2 polymorphisms in the promoter regions(c.1-1990T>C, c.1-693G>A) may affect on the CLCN channel function. The odds ratio for developing other IGE in patients with RS9820367-CG type was 4.2 compared to individuals with CC type. In addition, the odds ratio for developing other GEFSP in patients with RS9820367-CC type was 4.0 compared with individuals with CG type.
CONCLUSION
Our findings suggest that genomic variations of CLCN2 may be implicated in the pathogenesis of IGE.

Keyword

CLCN2; Mutation; Generalized epilepsy

MeSH Terms

Channelopathies
Chloride Channels
Clinical Coding
DNA
Epilepsy
Epilepsy, Generalized
Exons
Fires
gamma-Aminobutyric Acid
Genotype
Humans
Immunoglobulin E
Introns
Mutation, Missense
Odds Ratio
Polymerase Chain Reaction
Seizures
Seizures, Febrile
Chloride Channels
DNA
Epilepsy, Generalized
Immunoglobulin E
gamma-Aminobutyric Acid