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Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four‐year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available. [ABSTRACT FROM AUTHOR]

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 unreportedmutations. 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. [ABSTRACT FROM AUTHOR]