title: A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population.
abstract: Familial focal epilepsy with variable foci (FFEVF) is a heterogeneous epilepsy syndrome originally described in the French-Canadian (FC) population. Mutations in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in a wide spectrum of other familial focal epilepsies. In this study, we aimed to determine the frequency of mutation of this gene in our large cohort of FC individuals with FFEVF, as well as familial and sporadic cases with focal epilepsy. We report a recurrent p.R843X protein-truncating mutation segregating in one large FFEVF and two small focal epilepsy FC families. Fine genotyping suggests an ancestral allele. A new p.T864M variant, predicted to be disease-causing, was also identified in a small FC family. Overall, we identified DEPDC5 mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our results support the view that mutations in the DEPDC5 gene are an important cause of autosomal dominant focal epilepsies in the FC population, including a founder mutation that is specific to this population. These findings may facilitate molecular diagnosis in clinical practice.
authors.affiliation: CHUM Research Center, University of Montreal, Montreal, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Meloche
authors.forename: M-F
authors.initials: MF
authors.lastname: Rioux
authors.forename: D K
authors.initials: DK
authors.lastname: Nguyen
authors.forename: L
authors.initials: L
authors.lastname: Carmant
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: M
authors.initials: M
authors.lastname: Gravel
authors.forename: P
authors.initials: P
authors.lastname: Cossette
mesh_terms: D000293:Adolescent; D000328:Adult; D002170:Canada / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D004828:Epilepsies, Partial / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C000590398:DEPDC5 protein, human; D020690:GTPase-Activating Proteins; D012097:Repressor Proteins
keywords: epilepsy; familial focal epilepsy with variable foci; founder effect; mutation