title: Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12.
abstract: We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3. 8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (straight theta) 0 with D22S689. The LOD score in the larger family was 5.34 at straight theta=0 with the same marker. The two families share an identical linked haplotype for >/=10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF.
authors.affiliation: Centre Hospitalier de Université de Montréal, Hôpital Notre-Dame, Montréal, QC, H2L 4M1 Canada.
authors.forename: L
authors.initials: L
authors.lastname: Xiong
authors.forename: M
authors.initials: M
authors.lastname: Labuda
authors.forename: D S
authors.initials: DS
authors.lastname: Li
authors.forename: T J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: R
authors.initials: R
authors.lastname: Desbiens
authors.forename: G
authors.initials: G
authors.lastname: Patry
authors.forename: S
authors.initials: S
authors.lastname: Verret
authors.forename: P
authors.initials: P
authors.lastname: Langevin
authors.forename: S
authors.initials: S
authors.lastname: Mercho
authors.forename: M H
authors.initials: MH
authors.lastname: Seni
authors.forename: I
authors.initials: I
authors.lastname: Scheffer
authors.forename: F
authors.initials: F
authors.lastname: Dubeau
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: F
authors.initials: F
authors.lastname: Andermann
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: M
authors.initials: M
authors.lastname: Pandolfo
mesh_terms: D001315:Australia; D002170:Canada; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004828:Epilepsies, Partial / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D019683:Penetrance; D011110:Polymorphism, Genetic / Q000235:genetics; D018047:Receptors, Purinergic P1 / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D005819:Genetic Markers; D018047:Receptors, Purinergic P1