title: Mutations of DEPDC5 cause autosomal dominant focal epilepsies.
abstract: The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U975, Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Saeko
authors.initials: S
authors.lastname: Ishida
authors.forename: Fabienne
authors.initials: F
authors.lastname: Picard
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Eric
authors.initials: E
authors.lastname: Noé
authors.forename: Guillaume
authors.initials: G
authors.lastname: Achaz
authors.forename: Pierre
authors.initials: P
authors.lastname: Thomas
authors.forename: Pierre
authors.initials: P
authors.lastname: Genton
authors.forename: Emeline
authors.initials: E
authors.lastname: Mundwiller
authors.forename: Markus
authors.initials: M
authors.lastname: Wolff
authors.forename: Christian
authors.initials: C
authors.lastname: Marescaux
authors.forename: Richard
authors.initials: R
authors.lastname: Miles
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirsch
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baulac
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D019295:Computational Biology; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
chemical_list: D020662:Guanine Nucleotide Exchange Factors
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