Variants in SCN8A and Associated Genes in Saudi Arabian Epilepsy Cohort: A Preliminary Whole-Exome Sequencing Analysis

Background and Purpose: Epilepsy is a neurological disorder characterized by recurrent seizures, with genetic factors playing significant roles in its etiology. This preliminary study aimed to characterize genetic variants in Saudi Arabian epilepsy patients using whole‑exome sequencing (WES) data, providing exploratory insights into potential population‑specific patterns. 

Methods: Raw WES data (ERR10619203–ERR10619207) from five Saudi Arabian epilepsy patients were retrieved from the NCBI Sequence Read Archive (SRA). Data underwent quality control, alignment, and variant calling using standard bioinformatics workflows. Variants were annotated and classified according to American College of Medical Genetics and Genomics (ACMG) guidelines, with particular focus on established epilepsy‑associated genes. 

Results: The analysis identified 23,361 exonic variants across all genes. Within epilepsy‑associated genes, 3,005 variants were detected across 11 functional categories, with ion channel genes showing the highest variant burden (61%). Among sodium channel genes, SCN8A variants (n=87) appeared more frequent than SCN1A variants (n=12) in this small cohort. While this observation contrasts with patterns reported in other populations, the limited sample size precludes definitive conclusions. Additionally, analysis of GABRG2‑associated variants revealed genomic co‑localization with CCNG1 (n=343 variants), suggesting shared genomic regions rather than confirmed functional interaction. 

Conclusions: This exploratory analysis provides descriptive insights into the genetic landscape of epilepsy in a small Saudi Arabian cohort. The findings highlight possible population‑specific patterns but require validation in larger, more diverse samples. These preliminary results contribute to the growing understanding of geographical diversity in epilepsy genetics.