Abstract
Purpose Retinitis pigmentosa (RP) shows great diversity between genotypes and phenotypes, and it is important to identify the causative genes. This study aimed to analyze the molecular profiles, associated ocular characteristics, and progression of RP in Korean patients. Methods All the genetic variants in patients with RP, identified using targeted next-generation sequencing (NGS) with a panel of 88 RP-related genes between November 2018 and November 2019, were retrospectively reviewed. All the patients underwent comprehensive ophthalmological evaluations, and their clinical and family histories were recorded. The best-corrected visual acuity (BCVA) deterioration and photoreceptor disruption progression rates were determined based on the major causative mutational genes using nonlinear mixed models, and the differences among them were investigated using the interaction effect. Results Among the 144 probands, 82 variants in 24 causative genes were identified in 77 families (53.5%). Most of the RP cases were associated with autosomal recessive variants (N = 64 (44.4%)), followed by autosomal dominant (N = 10 (6.9%)) and X-linked variants (N = 3 (2.1%)). The four most frequently affected genes were EYS (N = 15 (10.4%)), USH2A (N = 12 (8.3%)), PDE6B (N = 9 (6.3%)), and RP1 (N = 8 (5.6%)). Epiretinal membranes and cystoid macular edema were frequently noted in the patients with USH2A (75.0%) and PDE6B (50.0%) variants, respectively. During the follow-up period, the BCVA and photoreceptor disruption changes were significantly different among the patients carrying the four common causative genes (P=0.014 and 0.034, resp.). Patients with PDE6B variants showed faster BCVA changes (0.2 LogMAR/10 years), and those with USH2A variants showed the fastest ellipsoid zone disruptions (−170.4 µm/year). Conclusion In conclusion, our genetic analysis using targeted NGS provides information about the prevalence of RP-associated mutations in Korean patients. Delineating clinical characteristics according to genetic variations may help clinicians identify subtype features and predict the clinical course of RP.
Highlights
Retinitis pigmentosa (RP, MIM#268000), which is the most common genetic retinopathy, is defined as a heterogeneous group of diseases that have various causes and unique mechanisms; each disease within this group results in the deterioration of vision [1]
All the detected variants were classified according to the American College of Medical Genetics and Genomics guidelines [9]. is study was conducted according to the tenets of the Declaration of Helsinki, and all the studyrelated data acquisitions were approved by the Institutional Review Board (IRB) of the Asan Medical Center (IRB No 2020-0859). e requirement for written informed consent was waived by the review board owing to the retrospective nature of the study. e results of each individual’s molecular analyses and ophthalmic examinations were recorded on an anonymized case report form that was verified by the IRB. e data recorded on these report forms were used in the final analyses
Autosomal recessive inheritance accounted for the largest proportion of RP cases (44.4%), followed by autosomal dominant (6.9%) and X-linked inheritance (2.1%); this overall pattern was similar to that observed in previous studies of individuals of Western and Eastern ethnicities [13, 14]
Summary
Retinitis pigmentosa (RP, MIM#268000), which is the most common genetic retinopathy, is defined as a heterogeneous group of diseases that have various causes and unique mechanisms; each disease within this group results in the deterioration of vision [1]. Several studies have evaluated the nationwide incidence of RP in Korea using population data from the Korean National Health Insurance System or from tertiary clinics. These studies were limited to reporting on the incidence, demographic characteristics, and ophthalmic characteristics of patients with RP [7, 8]. A genetic study was performed to determine the distribution of causative genes; the number of subjects in the study was relatively small, and the ability of the findings to represent the general genetic distribution in Korean patients with RP is limited [9]. We identified genetic profiles and associated clinical characteristics for several Korean patients with RP
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