Novel CERKL variant in consanguineous Jordanian pedigrees with inherited retinal dystrophies

Abstract Objective To identify the disease-causing variants in 2 families with autosomal recessive inherited retinal dystrophies (IRDs) and to characterize phenotypic variability across the affected family members. Design Exome sequencing and ophthalmic clinical examination study. Participants Six members from 2 consanguineous Jordanian families with IRD. Methods Ophthalmic examinations and whole-exome sequencing (WES) were performed to identify IRD-causing variants in affected individuals from each family, followed by segregation analysis of candidate variants in affected and unaffected family members by Sanger sequencing. Results We identified 2 different homozygous deletion variants in CERKL in each family: a novel pathogenic variant, c.450_451delAT, and a known variant, c.1187_1188delTG. Both variants co-segregated with the disease in all affected family members. The resulting phenotypes further supported that CERKL is associated with cone–rod dystrophy (CRD) rather than retinitis pigmentosa (RP), as originally established. Conclusion Our study expands the genotypic spectra of CERKL variants, providing insights into the relevant pathogenesis of RP/CRD. We also confirm that the WES approach is a valuable tool for the molecular diagnosis of retinopathies.