Molecular Genetic Characterization of Recurrent CRB1 and EIF2B5 Variants in an Iraqi Consanguineous Cohort with Inherited Retinal Dystrophy and White Matter Disease

Background: Inherited retinal dystrophy and inherited white matter disorders are genetically heterogeneous conditions in which consanguinity increases the probability of homozygous autosomal recessive variants. Objective: To characterize recurrent CRB1 and EIF2B5 variants in an anonymized Iraqi cohort using whole-exome sequencing and Sanger validation. Methods: The analyzed cohort consisted of 24 individuals: 10 unrelated unaffected controls, 6 patients with inherited retinal dystrophy, and 8 patients with white matter disease. Variant prioritization used phenotype-guided recessive filtering, Sanger confirmation, local-control comparison, and ACMG/AMP-oriented evidence mapping. Results: The retinal dystrophy group included 4 males and 2 females and showed a recurrent homozygous CRB1 variant, NM_201253.3:c.2106T>G; p.(Tyr702*), in all 6 cases and in none of the 10 controls. The white matter disease group included 4 males and 4 females and showed a recurrent homozygous EIF2B5 variant, c.327A>G; p.(Ile109Met), in all 8 cases and in none of the controls. Exact testing supported phenotype-specific separation from the controls for CRB1, EIF2B5, and combined affected status.