Abstracts

Recently, we mapped two susceptibility loci for photosensitivity (PPR) at 7q32 and 16p13 in 16 PPR-multiplex families with prominent myoclonic epilepsy background. The genes encoding for the metabotropic glutamate receptor 8 (GRM8) and the cholinergic-muscarinic type 2 acetylcholine receptor (CHRM2) participate in the neuromodulation of cortical dynamics and are located in the 7q32 region. To evaluate the relevance of these two high-ranking positional and functional candidate genes in the susceptibility for PPR in our families, we screened two patients from each family and four Dutch controls for mutations in the coding region, 100 bp of exon-intron boundaries, 5[apos] and 3[apos]untranslated regions and at least 600 bp of their promoter region. Direct sequencing of GRM8 and CHRM2 was performed on an automated ABI Prism 3730 sequencer using standard procedures and the sequences were analyzed and characterized using Vector NTI suite v8.0 and the viewer Artemis (release 6). We found novel variants not reported in the NCBI dbSNP, and detected several known variants which were also present in our Dutch controls. We are currently evaluating their familiar segregation and putative biological meaning. The variants identified may be useful to conduct future association studies. The identification of susceptibility gene for PPR would advance our understanding of epileptogenesis. (D. Pinto was supported by a grant from the Portuguese Ministry of Science and Technology (BD/ 1347/ 2000).)