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; Oirvar Eeg-Olofsson; Martha Feucht; Mogens Friis; Renzo Guerrini; Armin Heits; Marianne Kjeldsen; Rima Nabbout; Thomas Sander; Elaine Wirrell; Paul McKeigue; Robert Robinson; Nichole Taske; Mark Gardiner

doi:10.1016/j.eplepsyres.2007.05.004

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
, Oirvar Eeg-Olofsson
, Martha Feucht
, Mogens Friis
, Renzo Guerrini
, Armin Heits
, Marianne Kjeldsen
, Rima Nabbout
, Thomas Sander
, Elaine Wirrell
, Paul McKeigue

Robert Robinson, Nichole Taske, Mark Gardiner

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

43 Citations (Scopus)

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, a = 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 X((1))(2) = 5.17, p <0.03. Case-control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele:X((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 language	English
Pages (from-to)	145-153
Number of pages	9
Journal	EPILEPSY RESEARCH
Volume	75
Issue number	2-3
DOIs	https://doi.org/10.1016/j.eplepsyres.2007.05.004
Publication status	Published - Jul-2007

Keywords

childhood absence
epilepsy
linkage
association
mutation screening
CLCN2
IDIOPATHIC GENERALIZED EPILEPSIES
PEDIGREE DISEQUILIBRIUM TEST
GATED CHLORIDE CHANNEL
SELECTIVITY
CELLS
GENE

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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., Heits, A., Kjeldsen, M., Nabbout, R., Sander, T., Wirrell, E., ... Gardiner, M. (2007). Linkage and mutational analysis of CLCN2 in childhood absence epilepsy. EPILEPSY RESEARCH, 75(2-3), 145-153. https://doi.org/10.1016/j.eplepsyres.2007.05.004

@article{a7955ecec79b405f905e567581779322,

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, a = 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 X((1))(2) = 5.17, p <0.03. Case-control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele:X((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.(c) 2007 Elsevier B.V. All rights reserved.",

keywords = "childhood absence, epilepsy, linkage, association, mutation screening, CLCN2, IDIOPATHIC GENERALIZED EPILEPSIES, PEDIGREE DISEQUILIBRIUM TEST, GATED CHLORIDE CHANNEL, SELECTIVITY, CELLS, GENE",

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 Oirvar Eeg-Olofsson and Martha Feucht and Mogens Friis and Renzo Guerrini and Armin Heits and Marianne Kjeldsen and Rima Nabbout and Thomas Sander and Elaine Wirrell and Paul McKeigue and Robert Robinson and Nichole Taske and Mark Gardiner",

year = "2007",

month = jul,

doi = "10.1016/j.eplepsyres.2007.05.004",

language = "English",

volume = "75",

pages = "145--153",

journal = "EPILEPSY RESEARCH",

issn = "0920-1211",

publisher = "ELSEVIER SCIENCE BV",

number = "2-3",

}

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, Heits, A, Kjeldsen, M, Nabbout, R, Sander, T, Wirrell, E, McKeigue, P, Robinson, R, Taske, N & Gardiner, M 2007, 'Linkage and mutational analysis of CLCN2 in childhood absence epilepsy', EPILEPSY RESEARCH, vol. 75, no. 2-3, pp. 145-153. https://doi.org/10.1016/j.eplepsyres.2007.05.004

TY - JOUR

T1 - Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

AU - Everett, Kate

AU - Chioza, Barry

AU - Aicardi, Jean

AU - Aschauer, Harald

AU - Brouwer, Oebele

AU - Callenbach, Petra

AU - Covanis, Athanasios

AU - Dooley, Joseph

AU - Dulac, Olivier

AU - Durner, Martina

AU - Eeg-Olofsson, Oirvar

AU - Feucht, Martha

AU - Friis, Mogens

AU - Guerrini, Renzo

AU - Heits, Armin

AU - Kjeldsen, Marianne

AU - Nabbout, Rima

AU - Sander, Thomas

AU - Wirrell, Elaine

AU - McKeigue, Paul

AU - Robinson, Robert

AU - Taske, Nichole

AU - Gardiner, Mark

PY - 2007/7

Y1 - 2007/7

N2 - 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, a = 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 X((1))(2) = 5.17, p <0.03. Case-control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele:X((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.(c) 2007 Elsevier B.V. All rights reserved.

AB - 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, a = 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 X((1))(2) = 5.17, p <0.03. Case-control analysis provided evidence for a protective effect of the IVS4 + 12G > A minor allele:X((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.(c) 2007 Elsevier B.V. All rights reserved.

KW - childhood absence

KW - epilepsy

KW - linkage

KW - association

KW - mutation screening

KW - CLCN2

KW - IDIOPATHIC GENERALIZED EPILEPSIES

KW - PEDIGREE DISEQUILIBRIUM TEST

KW - GATED CHLORIDE CHANNEL

KW - SELECTIVITY

KW - CELLS

KW - GENE

U2 - 10.1016/j.eplepsyres.2007.05.004

DO - 10.1016/j.eplepsyres.2007.05.004

M3 - Article

SN - 0920-1211

VL - 75

SP - 145

EP - 153

JO - EPILEPSY RESEARCH

JF - EPILEPSY RESEARCH

IS - 2-3

ER -

Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

Abstract

Keywords

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