سجل مستودعي · ncbi-prjeb57558

Whole‐Exome Sequencing of a Saudi Epilepsy Cohort Reveals Association Signals in Known and Potentially Novel Loci

Background: Epilepsy, a serious chronic neurological condition effecting up to 100 million people globally, has clear genetic underpinnings including common and rare variants. In Saudi Arabia the prevalence of epilepsy is high and caused mainly by perinatal and genetic factors. No whole-exome sequencing (WES) studies have been performed to date in Saudi Arabian Epilepsy cohorts. This offers a unique opportunity for the discovery of rare genetic variants impacting this disease as there is a high rate of consanguinity amongst large tribal pedigrees. Results: We performed WES on 144 individuals diagnosed with epilepsy, to interrogate known Epilepsy related genes for known and functional novel variants. We also used an American College of Medical Genetics (ACMG) guideline based variant prioritization approach in an attempt to discover putative causative variants. We identified a 32 potentially causative pathogenic variants across 30 different genes in 44/144 (30%) of these Saudi Epilepsy individuals. We also identified 232 variants of unknown significance (VUS) across 101 different genes in 133/144 (92%) subjects. Strong enrichment of variants of likely pathogenicity were observed in previously described epilepsy-associated loci and a number of putative pathogenic variants in novel loci were also observed. Conclusion: Several putative pathogenic variants known to be epilepsy-related loci were identified for the first time in our population, in addition to several potential new loci which may be prioritized for further investigation.