Abstracts

RATIONALE: To identify more families with familial partial epilepsy with variable foci (FPEVF), which we recently mapped on chromosome 22q12; to define a minimum genetic distance within the region; and eventually identify the causative gene mutation. METHODS:We evaluated and genotyped more families with multiple cases of partial epilepsy for possible linkage to 22q12, determined the disease haplotype and recombination events across the region, by using polymorphic microsatellite markers and SNPs (single nuleotide polymorphism). We further evaluated several candidate genes within the critical region by mutation analysis and direct sequencing. RESULTS: In addition to the original two French-Canadian families, five more French-Canadian and one Spanish families presenting with FPEVF showed evidence of linkage to 22q12. All affected individuals have mainly nocturnal partial seizures arising from frontal, temporal or occipital regions. All neuroligical examinations and neuroimaging studies are normal, except for homozygous affected individuals, which have a more severe phenotype. 7 French-Canadian families share the same disease haplotype in a 2.5 Mb region on chromosome 22q12. The Spanish family presents with a different disease-associated haplotype. Several possible candidate genes, including the brain-specific ? isoform of 14.3.3 protein, synapsin III, have been excluded by recombination detection, mutation analysis and direct sequencing. CONCLUSIONS:FPEVF is a new autosomal dominant idiopathic partial epilepsy syndrome characterized by mainly nocturnal partial seizures arising from different brain areas in different affected individuals within one family. A gene determining FPEVF is localized to a ?2.5 Mb interval on chromosome 22q12. Two different FPEVF-associated haplotypes originated from French-Canadian and Spanish population suggest two independent mutations in the same gene.