The clinical phenotypes and genetic characteristics of seven epilepsy patients related to heterozygous DEPDC5 variants in China

Objective:DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin(mTOR)pathway.Deregulation of mTOR signalling has been associated to various neurological conditions,including epilepsy.Variants in the gene encoding GATOR1 complex,especially in DEPDC5,have been implicated in the pathogensis of several focal epilepsies.While there was little report on the electroencephalogram(EEG)feature of DEPDC5 related epilepsy,we decided to investigate the specific EEG pattern and the prognosis of DEPDC5 related epilepsy.Methods:The records of 546 epilepsy patients with unknown causes who were admitted in Xijing Hospital and underwent whole exome sequencing(WES)from 2015 to 2019 were retrospectively reviewed.Finally,the clinical data of these 7 patients with DEPDC5 variants were collected in this study.We analyzed their clinical manifestations,EEG and magnetic resonance imaging(MRI).Results:Seven DEPDC5 variants,including six novel mutations,were identified in seven individuals with focal epilepsy.Among these patients,one had family history.Four showed specific interictal EEG patterns,periodic-like sharp waves or spike waves,were found in four patients.Five out of seven patients(71.4%)were well-controlled by anti-epilepsy drugs while two patients with sleep-related hypermotor epilepsy had either drug resistance or relapse of epilepsy.Conclusion:DEPDC5 variants were related to focal epilepsy in patients with or without family history.The EEG abnormalities of DEPDC5 related epilepsy were heterogeneous among different patients,while periodic-like sharp waves or spike waves might be the most characteristic interictal EEG pattern for DEPDC5 related epilepsies.In this study the prognosis of DEPDC5 related epilepsy was similar to other epilepsies.DEPDC5 variants may not predict the prognosis so far.