Mapping of a gene determining familiar partial epilepsy with variable focito chromosome 22q11-q12

We identified two large French-Canadian families segregating a familial par tial epilepsy syndrome with variable foci (FPEVF) characterized by mostly n octurnal seizures arising from frontal, temporal, and occasionally occipita l epileptic foci. There is no evidence for structural brain damage or perma nent neurological dysfunction. The syndrome is inherited as an autosomal do minant trait with incomplete penetrance. We mapped the disease locus to a 3 .8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S68 5. Using the most conservative diagnostic scheme, the maximum cumulative LO D score was 6.53 at recombination fraction (theta) 0 with D22S689. The LOD score in the larger family was 5.31 at theta = 0 with the same marker. The two families share an identical linked haplotype for greater than or equal to 10 cM, including the candidate interval, indicating a recent founder eff ect. A severe phenotype in one of the probands may be caused by homozygosit y for the causative mutation, as suggested by extensive homozygosity for th e linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, in dicating genetic heterogeneity of FPEVF.