Everett, KV;
Chioza, B;
Aicardi, J;
Aschauer, H;
Brouwer, O;
Callenbach, P;
Covanis, A;
... Gardiner, M; + view all
(2007)
Linkage and association analysis of CACNG3 in childhood absence epilepsy.
EUR J HUM GENET
, 15
(4)
463 - 472.
10.1038/sj.ejhg.5201783.
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Abstract
Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5 - 4 Hz spike - wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12 - p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD 3.54, a 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum nonparametric linkage score was 2.87 (P > 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP- based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P <= 0.01) was found for SNPs within a similar to 35 kb region of high LD encompassing the 5'UTR, exon 1 and part of intron 1 of CACNG3. Re-sequencing of this interval was undertaken in 24 affected individuals. Seventy-two variants were identified: 45 upstream; two 5'UTR; and 25 intronic SNPs. No coding sequence variants were identified, although four variants are predicted to affect exonic splicing. This evidence supports CACNG3 as a susceptibility locus in a subset of CAE patients.
| Type: | Article |
|---|---|
| Title: | Linkage and association analysis of CACNG3 in childhood absence epilepsy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/sj.ejhg.5201783 |
| Publisher version: | http://ukpmc.ac.uk/abstract/MED/17264864 |
| Keywords: | absence epilepsy, linkage, association, CACNG3, splice variants, IDIOPATHIC GENERALIZED EPILEPSY, PEDIGREE DISEQUILIBRIUM TEST, GENETIC-VARIATION, SEIZURES, CHANNEL, CACNA1H, MOUSE, MUTATIONS, RECEPTORS, VARIANTS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/8218 |
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