Abstract
Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1, causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.
Trial registration:
ClinicalTrials.gov NCT03281005 NCT04868916.
Keywords:
CRX; GUCY2D; RP1L1; miyake disease; non-RP1L1; occult macular dystrophy.
Publication types
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Cohort Studies
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East Asian People
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Electroretinography
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Eye Proteins / genetics
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Humans
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Macular Degeneration* / pathology
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Retina / pathology
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Retinal Dystrophies* / pathology
Substances
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RP1L1 protein, human
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Eye Proteins
Associated data
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ClinicalTrials.gov/NCT03281005
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ClinicalTrials.gov/NCT04868916
Grants and funding
This research was funded by grants from Grant-in-Aid for Young Scientists of the Ministry of Education, Culture, Sports, Science and Technology, Japan (18K16943), grants from JSPS KAKENHI Grant Numbers 21J21086, 22KJ2665 (Research Fellowships for Young Scientists (DC1), Japan), grants from Japan Agency for Medical Research and Development (AMED), grants from the Ministry of Health, Labor and Welfare, Japan (18ek0109282h0002, 23ek0109634h0001, 23ek0109632h0001), grants from Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Japan (H26-26462674), Health Labour Sciences Research Grant (23FC1056), grant from National Institute of Health and Care Research (AI AWARD 02488), grants from Foundation Fighting Blindness (CD-CL-0214-0631-PUMCH); CAMS Innovation Fund for Medical Sciences, China, CIFMS 2016-12M-1-002; National Natural Science Foundation of China, China, 81470669, Seoul National University Bundang Hospital (SNBH) research grant: 02-2017-059; National Research Foundation (NRF) of Korea grant: RS-2023-00248480; grants from Grant-in-Aid for Young Scientists (A) of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16H06269), grants from Grant-in-Aid for Scientists to support international collaborative studies of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16KK01930002), grants from National Hospital Organization Network Research Fund, Japan (H30-NHO-Sensory Organs-03), grants from FOUNDATION FIGHTING BLINDNESS ALAN LATIES CAREER DEVELOPMENT PROGRAM (CF-CL-0416-0696-UCL), USA, grants from Health Labour Sciences Research Grant, AMED (23EK0109634H0001, 23EK0109632H0001), The Ministry of Health Labour and Welfare, Japan (201711107A, 23809955), and grants from Great Britain Sasakawa Foundation Butterfield Awards, UK.