Abstracts

Rationale: DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently been reported in a broad spectrum of inherited focal epilepsies. We discovered a multiplex epilepsy family affected by autosomal dominant focal epilepsy, who shared the DEPDC5 gene mutation of matching site. Methods: A 5 year old boy presented with focal seizure involving left eyelid and left leg. The patient had family history, as his father and father’s close relatives were suffering from epilepsy. Under suspicion of inherited focal epilepsy syndrome the patient’s family members were tested with targeted epilepsy gene panel sequencing. Results: The patient, patient’s father and patient’s younger brother were found to share a novel splice site mutation (NM_001242896; c.4520-1G>A) within exon 43 of DEPDC5. The mutation was confirmed to be shared in other relatives from paternal side.This mutation caused focal epilepsy syndome similar  to previously described familial focal epilepsy with variable foci (FFEVF). The penetrance in our family was variable, as two mutation carriers were asymptomatic. Family members who had their brain MRI done showed normal findings except one patient who showed mild right hippocampal atrophy. Treatment responses to antiepileptic agents were also variable among family members.  Conclusions: Our study report a novel mutation of DEPDC5 gene in a multiplex family with FFEVF, and it is the first report of the mutation in Korean family. The variable epilepsy phenotypes among family members sharing same mutation suggest that there may be dissociation between the seizure initiation mechanism and the underlying genetic mechanism.    Funding: We received no fundings for this abstract.