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| Item Type: | Article |
|---|---|
| Title: | Linkage and association analysis of CACNG3 in childhood absence epilepsy |
| Creators Name: | Everett, K.V., Chioza, B., Aicardi, J., Aschauer, H., Brouwer, O., Callenbach, P., Covanis, A., Dulac, O., Eeg-Olofsson, O., Feucht, M., Friis, M., Goutieres, F., Guerrini, R., Heils, A., Kjeldsen, M., Lehesjoki, A.E., Makoff, A., Nabbout, R., Olsson, I., Sander, T., Siren, A., McKeigue, P., Robinson, R., Taske, N., Rees, M. and Gardiner, M. |
| 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, alpha=0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric 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 approximately 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. |
| Keywords: | Absence epilepsy, Linkage, Association, CACNG3, Splice variants |
| Source: | European Journal of Human Genetics |
| ISSN: | 1018-4813 |
| Publisher: | Nature Publishing Group |
| Volume: | 15 |
| Number: | 4 |
| Page Range: | 463-472 |
| Date: | April 2007 |
| Official Publication: | https://doi.org/10.1038/sj.ejhg.5201783 |
| PubMed: | View item in PubMed |
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