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 among 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 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 was observed in previously described epilepsy-associated loci, and a number of putative pathogenic variants in novel loci are also observed. CONCLUSION: Several putative pathogenic variants in known 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.

Impact of depression and fatigue on relapsing remitting multiple sclerosis in Kingdom of Saudi Arabia.

OBJECTIVES: To determine relationship between fatigue, depression with the registration in multiple sclerosis (MS) society activity, and stress with the risk developing a new attack in patients with Relapsing remitting MS (RRMS) in the Kingdom of Saudi Arabia (KSA). METHODS: This was a cohort retrospective study conducted in the KSA between July 2018 and July 2019 which included a total of 465 RRMS patients. Data were collected during interviews using the Beck Depression Inventory (BDI) and Modified Fatigue Impacts Scale (MFIS). Demographic and clinical data were also collected. RESULTS: Of 465 participants, 317 expressed psychological stress before the last attack, 67 of whom developed an attack within 4 weeks, and 250 of whom developed an attack after 4 weeks. Significantly lower BDI scores were associated with registration in MS associations (p=0.003, df = 5). Significantly lower MFIS scores were associated with registration in MS associations (p=0.001, df = 5). CONCLUSION: The majority of RRMS patients have a significant fatigue and depression, and there are significant relationships between registration in the MS society and MFIS and BDI scores where patients who officially registered in MS society have lower score in MFIS and BDI. we recommend regular follow-ups with a psychologist and/or registration with MS societies.