Clinical application of whole-exome sequencing analysis in childhood epilepsy

The swift updates of public databases and advancements in next-generation sequencing (NGS) technologies have enhanced the genetic identification capacities of epilepsy clinics. This study aimed to evaluate the diagnostic efficacy of NGS in pediatric epilepsy patients as a whole and to present the data obtained in the whole exome sequence analysis. We enrolled 40 children with suspected childhood epilepsy in this study. All patients underwent evaluation by a clinical geneticist or pediatric neurologist and the molecular genetic analysis of those children was performed by whole-exome sequencing (WES). Out of the 40 patients, 12 (30%) received a genetic diagnosis, involving 14 mutations across 13 genes. The cumulative positive diagnostic yield was 30%. Twelve of these patients were identified to have 5 variants previously documented as pathogenic, 9 variants classified as likely pathogenic, and 5 novel variants that have not been reported before. The outcomes indicate that whole-exome sequencing offers great benefits in clinical patient diagnosis, particularly in terms of detecting diagnostic variants. This study underscored the significance of whole exome sequencing (WES) studies, where only a broad gene set is examined in epilepsy patients. This approach has the potential to establish gene-specific phenotypic profiles, particularly by uncovering novel candidate genes in epilepsy patients with well-defined phenotypes. Additionally, conducting validation studies on variants of uncertain clinical significance could enhance the outcome yield.