Novel CERKL variant in consanguineous Jordanian pedigrees with inherited retinal dystrophies.

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.