The Utility of Whole Exome Sequencing in Diagnosing Neurogenetic Disorders: UAE Experience

Abstract

Abstract Background The application of whole exome sequencing (WES) served as a helpful tool in the diagnosis of neurological disorders. Aim We aimed at investigating the diagnostic yield of WES in obtaining a molecular confirmation of neurogenetic disorders and identifying novel disease-causing variants in a highly consanguineous population. Methods This is a retrospective multicenter study that included pediatric patients presenting to the neurology and genetic clinics with neurological disorders who underwent WES across four cities in the United Arab Emirates (UAE). The patient's charts were reviewed in detail during the period from December 2019 to December 2022 for the core clinical features, analysis of the molecular data, and recording of the previously unreported mutations. Results 338 patients were enrolled of which 71% wereconsanguineous. Their main clinical presentation was developmental delay (78.3%), seizures (55%), distinctive facial features (42.9%), behavioral abnormalities (36.9%) and weakness (25.7%), respectively. Disease-causing variants were identified in 57.1%, of which half of them (50.1%) showed novel mutations. 4.6% of candidate genes have not been linked to human diseases yet and 7.8% of potentially treatable disorders were reported. Conclusion We report a high yield from WES in a highly consanguineous population, where almost a third of our patients showed novel variants for neurogenetic disorders. Potentially treatable disorders were described highlighting its importance in modifying the treatment plan and offering better knowledge and standards of care. We also spotted candidate genes that can potentially be novel genes associated with previously undescribed new syndromes. However, further cases are needed to confirm this gene- disease relationship.