title: Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
abstract: The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) is notable because family members have seizures originating from different cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction.
authors.affiliation: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia. leanne.dibbens@unisa.edu.au
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Boukje
authors.initials: B
authors.lastname: de Vries
authors.forename: Simona
authors.initials: S
authors.lastname: Donatello
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.forename: Bree L
authors.initials: BL
authors.lastname: Hodgson
authors.forename: Satyan
authors.initials: S
authors.lastname: Chintawar
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Crompton
authors.forename: James N
authors.initials: JN
authors.lastname: Hughes
authors.forename: Susannah T
authors.initials: ST
authors.lastname: Bellows
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Klein
authors.forename: Petra M C
authors.initials: PM
authors.lastname: Callenbach
authors.forename: Mark A
authors.initials: MA
authors.lastname: Corbett
authors.forename: Alison E
authors.initials: AE
authors.lastname: Gardner
authors.forename: Sara
authors.initials: S
authors.lastname: Kivity
authors.forename: Xenia
authors.initials: X
authors.lastname: Iona
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Regan
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Weller
authors.forename: Denis
authors.initials: D
authors.lastname: Crimmins
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerrero-López
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Francois
authors.initials: F
authors.lastname: Dubeau
authors.forename: Laura
authors.initials: L
authors.lastname: Licchetta
authors.forename: Francesca
authors.initials: F
authors.lastname: Bisulli
authors.forename: Patrick
authors.initials: P
authors.lastname: Cossette
authors.forename: Paul Q
authors.initials: PQ
authors.lastname: Thomas
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Jose
authors.initials: J
authors.lastname: Serratosa
authors.forename: Oebele F
authors.initials: OF
authors.lastname: Brouwer
authors.forename: Frederick
authors.initials: F
authors.lastname: Andermann
authors.forename: Eva
authors.initials: E
authors.lastname: Andermann
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019295:Computational Biology; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010375:Pedigree; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C000590398:DEPDC5 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D012097:Repressor Proteins
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