Investigation of copy number variations in epilepsy

Epilepsy is defined as a common neurological disorder characterized by recurrent seizures resulting from abnormal, excessive, and synchronous electrical discharges in a population of neurons. It has been reported to affect more than 50 million people worldwide, with a crude prevalence of approximately 7.6 per 1000 individuals. Although epilepsy arises from genetic, structural, infectious, metabolic, immune, and unknown causes, 40–60% of cases have been shown to be genetic in origin. Current studies have identified insertion/deletion (indel) and single-nucleotide variants (SNVs) in approximately 300 genes directly implicated in epileptogenesis; moreover, more than 500 epilepsy genes related to neurodevelopmental processes have been reported. In addition, copy-number variants (CNVs) have been shown to play a significant role in epileptogenesis, and their frequency has been reported to range between 5% and 12% across different epilepsy subtypes. In this study, whole-exome sequencing (WES) data from 102 epilepsy patients who remained undiagnosed after short-variant analysis were reprocessed to investigate CNVs. Bioinformatic analyses and molecular validation identified CNVs in 8 patients that could account for the clinical phenotype.