DEPDC 5 mutations are not a frequent cause of familial temporal lobe epilepsy

Summary Mutations in the DEPDC 5 ( 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 DEPDC 5 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 DEPDC 5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC 5 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 DEPDC 5 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.