BACKGROUND: Variants in the DEPDC5 have been proved to be main cause of not only various dominant familial focal epilepsies, but also sporadic focal epilepsies. In the present study, a novel variant in DEPDC5 was detected in the patient with focal epilepsy and his healthy father. We aimed to analyze the pathogenic DEPDC5 variant in the small family of three.
METHODS: A 5-month-old male infant presented with focal epilepsy. Whole exome sequencing identified a novel heterozygous variant c.1696delC (p.Gln566fs) in DEPDC5, confirmed by Sanger sequencing. The variant was inherited from healthy father.
CONCLUSIONS: Our study expands the spectrum of DEPDC5 variants. Moreover, We discuss the relation between the low penetrance of DEPDC5 and the relatively high morbidity rate of DEPDC5-related sporadic focal epilepsy. Besides, due to interfamilial phenotypic and genetic heterogeneity, we speculate the prevalence of familial focal epilepsy with variable foci might be underestimated in such small families. We emphasize the importance of gene detection in patients with sporadic epilepsy of unknown etiology, as well as their family members. It can identify causative mutations, thus providing help to clinicians in making a definitive diagnosis.

Mutations in the disheveled, Egl-10 and domain-containing protein 5 (DEPDC5) recently have been identified as a common cause of focal epilepsy syndromes. The association between phenotype and genotype of DEPDC5 mutation has not been adequately characterized. We studied four families with familial focal epilepsy carrying DEPDC5 mutations. Four novel DEPDC5 mutations were identified by next-generation sequencing, including two missense mutations (c.1729 >A and c.3260G>A), one splicing mutation (c.280-1G>A), and one frameshift mutation (c.515_516delinsT). We found that patients carrying different DEPDC5 mutation have different clinical manifestations. Incomplete penetrance is a prominent feature of DEPDC5-related epilepsy, with the rate of penetrance ranging from 25 to 100%. About 21.4% of patients with DEPDC5-related familial focal epilepsy are refractory to treatments. We further reviewed the correlation of genotype and phenotype in all previous literature regarding DEPDC5-related epilepsy. Our study suggested that the type of DEPDC5 mutation might provide important information for the prognosis evaluation.