@article{b6707c66a5994325812f1fa20613f8b4,
title = "Linkage and mutational analysis of CLCN2 in childhood absence epilepsy",
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, 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.",
keywords = "Association, CLCN2, Childhood absence epilepsy, Linkage, Mutation screening",
author = "Kate Everett and Barry Chioza and Jean Aicardi and Harald Aschauer and Oebele Brouwer and Petra Callenbach and Athanasios Covanis and Joseph Dooley and Olivier Dulac and Martina Durner and Orvar Eeg-Olofsson and Martha Feucht and Mogens Friis and Renzo Guerrini and Armin Heils and Marianne Kjeldsen and Rima Nabbout and Thomas Sander and Elaine Wirrell and Paul McKeigue and Robert Robinson and Nichole Taske and Mark Gardiner",
note = "Funding Information: This work was supported by the Medical Research Council (UK), Wellcome Trust, Action Medical Research and Epilepsy Research Foundation. We are very grateful to the families for participating in this study and to all our 142 collaborating clinicians, including Drs. Andrew Makoff, Lina Nashef, Auli Sir{\'e}n, Ingrid Olsson and Anna-Elina Lehesjoki. We would like to thank G{\'e}n{\'e}thon for their assistance in collecting the French samples. Austrian financial support came from the Austrian Research Foundation (awarded to Harald Aschauer, MD), grant number P10460-MED. Thomas Sander, MD, was awarded a grant by the Deutsche Forschungsgemeinschaft (Sa434/3-1), the German National Genome Research Network (01GS0479). Dutch financial support came from the Netherlands Organisation for Health, Research and Development (ZonMW, 940-33-030) and the Dutch National Epilepsy Fund—{\textquoteleft}The power of the small{\textquoteright} (NEF—{\textquoteleft}De macht van het kleine{\textquoteright}, 98-14). Danish support (Mogens L. Friis, MD and Marianne Kjeldsen, MD) came from the NINDS grant (NS-31564). Martina Durner, MD was supported by NINDS grant number NS37466. The experiments involved in this study comply with the current laws of the country in which they were performed.",
year = "2007",
month = jul,
doi = "10.1016/j.eplepsyres.2007.05.004",
language = "English (US)",
volume = "75",
pages = "145--153",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",
number = "2-3",
}