Belal Azab1, Raghda Barham2, Dema Ali2, Zain Dardas2, Lana Rashdan2, Maysa Bijawi2, Ranad Maswadi3, Abdelhalim Awidi2, Hanan Jafar2, Mohammed Abu-Ameerh4, Muawyah Al-Bdour4, Sami Amr5, Abdalla Awidi6. 1. Cell Therapy Center, The University of Jordan, Amman, Jordan; Clinical Laboratory Sciences Department, School of Science, The University of Jordan, Amman, Jordan. Electronic address: b.azab@ju.edu.jo. 2. Cell Therapy Center, The University of Jordan, Amman, Jordan. 3. London School of Hygiene and Tropical Medicine, London, United Kingdom. 4. Ophthalmology Department, Jordan University Hospital, The University of Jordan, Amman, Jordan. 5. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 6. Cell Therapy Center, The University of Jordan, Amman, Jordan; Department of Medicine and Hematology, Jordan University Hospital, The University of Jordan, Amman, Jordan.. Electronic address: abdalla.awidi@gmail.com.
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.
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.