Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

Tools

Item Type:	Article
Title:	Linkage and mutational analysis of CLCN2 in childhood absence epilepsy
Creators Name:	Everett, K., Chioza, B., Aicardi, J., Aschauer, H., Brouwer, O., Callenbach, P., Covanis, A., Dooley, J., Dulac, O., Durner, M., Eeg-Olofsson, O., Feucht, M., Friis, M., Guerrini, R., Heils, A., Kjeldsen, M., Nabbout, R., Sander, T., Wirrell, E., McKeigue, P., Robinson, R., 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
ISSN:	0920-1211
Publisher:	Elsevier
Volume:	75
Number:	2-3
Page Range:	145-153
Date:	July 2007
Official Publication:	https://doi.org/10.1016/j.eplepsyres.2007.05.004
PubMed:	View item in PubMed

Repository Staff Only: item control page