Linkage and mutational analysis of CLCN2 in childhood absence epilepsy
2007 (English)In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 75, no 2-3, 145-153 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 75, no 2-3, 145-153 p.
Association, Childhood absence epilepsy, CLCN2; Linkage, Mutation screening
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-14386DOI: 10.1016/j.eplepsyres.2007.05.004ISI: 000248904200009PubMedID: 17580110OAI: oai:DiVA.org:uu-14386DiVA: diva2:42156