Abstracts

In linkage genome scans of Idiopathic Generalized Epilepsy (IGE) we found evidence for linkage on chromosome 5p with the juvenile absence phenotype. There are at least two candidate genes in this region: Succinate dehydrogenase complex subunit A (SDHA) and Programmed cell death 6 (PDCD6)., We examined this region for association with Juvenile Absence Epilepsy (JAE) and Childhood Absence Epilepsy (CAE), genotyping single nucleotide polymorphisms in and around SDHA and PDCD6. We used case-control and family-based association methods to determine the degree of association., We found that CAE is strongly associated with all SNPs tested in the PDCD6 gene (maximum chi-squared = 21.22, p[lt]0.0001 at rs4957014). JAE, in contrast, was not significantly associated with PDCD6 or any SNPs in the region studied. These results were confirmed in the family-based association analysis. The odds of having CAE if one carries at least one copy of the associated allele at the rs4957014 locus is 3.2 times the odds for an individual without a copy of the allele at this locus (95%CI: 1.91 [ndash] 5.37)., Our results suggest that not only does PDCD6 play a role in CAE susceptibility, but that different genes contribute to susceptibility in CAE and JAE; no association was seen in the JAE group. This implies that CAE and JAE cannot necessarily be treated as having the same genetic basis. Although there may be susceptibility genes common to the two (or more) syndromes, treating them as one genetic entity could mask the existence of genes for only one of the syndromes. It is especially interesting that this is at least the second apoptosis gene that appears to be related to a form of IGE.
We wish to acknowledge our many collaborators who were critical to this study. Space limitations make it impossible to name them here., (Supported by NIH RO1 NS37466 (to MD) and NIH RO1 NS027941 (to DAG).)