Linkage and mutational analysis of CLCN2 in childhood absence epilepsy
- 作者：Kate Everett ; Barry Chioza ; Jean Aicardi ; Harald Aschauer ; Oebele Brouwer ; Petra Callenbach ; Athanasios Covanis ; Joseph Dooley ; Olivier Dulac ; Martina Durner ; Orvar Eeg-Olofsson ; Martha Feucht ; Mogens
- 关键词：Childhood absence epilepsy ; Linkage ; Association ; Mutation screening ; CLCN2
- 刊名：Epilepsy Research
- 出版年：2007
- 期刊代码：87_09201211
- 类别：med
- 出版时间：July 2007
- 卷：75
- 期：2-3
- 页码：145-153
- 文件大小：690 K
摘要
In order to assess the chloride channel gene CLCN2 as a candidate susceptibility gene for childhood absence epilepsy, parametric and non-parametric linkage analysis was performed in 65 nuclear pedigrees. This provided suggestive evidence for linkage with heterogeneity: NPL score = 2.3, p < 0.009; HLOD = 1.5, α = 0.44. Mutational analysis of the entire genomic sequence of CLCN2 was performed in 24 unrelated patients from pedigrees consistent with linkage, identifying 45 sequence variants including the known non-synonymous polymorphism rs2228292 (G2154C, Glu718Asp) and a novel variant IVS4 + 12G > A. Intra-familial association analysis using the pedigrees and a further 308 parent–child trios showed suggestive evidence for transmission disequilibrium of the G2154C minor allele: AVE-PDT 
, p < 0.03. Case–control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele: 
, p < 0.008. The 65 nuclear pedigrees were screened for three previously identified mutations shown to segregate with a variety of idiopathic generalised epilepsy phenotypes (597insG, IVS2-14del11 and G2144A) but none were found. We conclude that CLCN2 may be a susceptibility locus in a subset of cases of childhood absence epilepsy.