Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

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 McKeigueRobert Robinson, Nichole Taske, Mark Gardiner

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 χ(1)2 = 5.17, p < 0.03. Case-control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele: χ(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.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalEpilepsy Research
Issue number2-3
StatePublished - Jul 2007


  • Association
  • CLCN2
  • Childhood absence epilepsy
  • Linkage
  • Mutation screening

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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