PubMed 17580110

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC2 , ClvC4

Title: Linkage and mutational analysis of CLCN2 in childhood absence epilepsy.

Authors: 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 Friis, Renzo Guerrini, Armin Heils, Marianne Kjeldsen, Rima Nabbout, Thomas Sander, Elaine Wirrell, Paul McKeigue, Robert Robinson, Nichole Taske, Mark Gardiner

Journal, date & volume: Epilepsy Res., 2007 Jul , 75, 145-53

PubMed link:

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.