Using Exome Sequencing to Identify the Causes of Neurodevelopmental Disorders: Experience of a North African Genetic...

Although exome sequencing (ES) is not widely implemented in some countries due to financial constraints, it represents an effective approach for the genetic diagnosis of neurodevelopmental disorders (NDDs). We report ES results from a North African cohort of 168 unrelated patients with NDDs referred for diagnostic testing. Patients were classified into three clinical categories: isolated NDDs (29%), NDDs associated with epilepsy (17%), and NDDs with dysmorphic features (54%). The consanguinity rate was 63%. ES identified pathogenic or likely pathogenic variants (71 SNVs and 5 CNVs) in 75 patients, corresponding to a diagnostic yield of 45%. Variants of uncertain significance were detected in 66 cases (39%). Among pathogenic/likely pathogenic findings, variants were predominantly homozygous (39 out of 42 autosomal recessive cases), followed by heterozygous variants associated with autosomal dominant inheritance (29 cases) and hemizygous X-linked variants (5 cases). In conclusion, ES demonstrated a high diagnostic yield in this cohort, supporting its value as a diagnostic tool for NDDs, particularly in highly consanguineous populations.