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Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

Item Type:Article
Title:Linkage and mutational analysis of CLCN2 in childhood absence epilepsy
Creators Name:Everett, K. and Chioza, B. and Aicardi, J. and Aschauer, H. and Brouwer, O. and Callenbach, P. and Covanis, A. and Dooley, J. and Dulac, O. and Durner, M. and Eeg-Olofsson, O. and Feucht, M. and Friis, M. and Guerrini, R. and Heils, A. and Kjeldsen, M. and Nabbout, R. and Sander, T. and Wirrell, E. and McKeigue, P. and Robinson, R. and Taske, N. and Gardiner, M.
Abstract: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, {alpha}=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 {chi}(1)2 = 5.17, p<0.03. Case-control analysis provided evidence for a protective effect of the IVS4+12G>A minor allele: {chi}(1)2 = 7.27, 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.
Keywords:Childhood Absence Epilepsy, Linkage, Association, Mutation Screening, CLCN2
Source:Epilepsy Research
Page Range:145-153
Date:July 2007
Official Publication:https://doi.org/10.1016/j.eplepsyres.2007.05.004
PubMed:View item in PubMed

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