title: DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.
abstract: Mutations in the DEPDC5 (DEP domain-containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12-37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies.
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: CNR-Neuroscience Institute, Section of Padua, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Serioli
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, School of Medicine, Federico II University, Napoli, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Santulli
authors.affiliation: Institute of Molecular Bioimaging and Physiology, Section of Germaneto, National Research Council, Catanzaro, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Manna
authors.affiliation: Institute of Molecular Bioimaging and Physiology, Section of Germaneto, National Research Council, Catanzaro, Italy.|Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.affiliation: CNR-Neuroscience Institute, Section of Padua, Padova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Dazzo
authors.affiliation: IRCCS-Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pasini
authors.affiliation: Institute of Molecular Bioimaging and Physiology, Section of Germaneto, National Research Council, Catanzaro, Italy.|Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: IRCCS-Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Michelucci
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, School of Medicine, Federico II University, Napoli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.affiliation: CNR-Neuroscience Institute, Section of Padua, Padova, Italy.|Department of Biomedical Sciences, University of Padua, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005192:Family Health; D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C000590398:DEPDC5 protein, human; D020690:GTPase-Activating Proteins; D012097:Repressor Proteins
keywords: Familial focal epilepsy with variable foci; Genetics; Mutation; Temporal lobe seizures