Clinical Exome-Based Redefinition and Reclassification of Retinitis Pigmentosa.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP.

Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns.

Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, was the most common causative gene (14/60, 23.3%), followed by (13/60, 21.7%) and (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in , and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and and were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti's crystalline dystrophy, with identified as the causative gene. In another patient (1/60, 1.7%), variants were detected with clinical findings suggestive of cone-rod dystrophy.

Conclusion: This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.