Abstracts

Rationale: DEPDC5 loss-of-function mutations have been identified in 12% of genetic focal epilepsies and in 13% of autosomal dominant nocturnal frontal lobe epilepsy families. We aimed to study the prevalence of DEPDC5 mutations in 62 Italian families with recurrence of temporal lobe epilepsy. Methods: Families with recurrence of temporal lobe epilepsy were recruited at several epilepsy centers participating in a project supported by the Genetics Commission of the Italian League Against Epilepsy (LICE). Whole exome sequencing were performed in 18 probands and targeted next generation sequencing (NGS) of the DEPDC5 gene in 44 probands. Results: The study pedigrees included 31 families with at least two members with lateral temporal epilepsy (ADLTE families) without LGI1 mutations, 14 families with at least two members with mesial temporal lobe epilepsy (FMTLE families), and 17 families with mixed lateral, mesial, and other focal epilepsies. Targeted NGS identified a non-sense mutation, c.918C>G (p.Y306X), in a small family diagnosed as FMTLE, resulting in a truncated protein product. No other mutations were identified. Conclusions: Our results suggest that the percentage of DEPDC5 mutations in familial temporal lobe epilepsies may be lower than in other genetic focal epilepsies. Particularly, mutations in this gene may be absent in ADLTE. The small size of the mutated pedigree suggests that it may actually be part of a broader kindred with familial focal epilepsy with variable foci phenotype.