Journal
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
Volume 9, Issue 6, Pages -Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/tvst.9.6.2
Keywords
macular dystrophy; cone rod dystrophy; GUCY2D; autosomal dominant; Leber congenital amaurosis
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [16H06269, 16KK01930002, 18K16943]
- National Hospital Organization Network Research Fund [H30-NHO-Sensory Organs-03]
- FOUNDATION FIGHTING BLINDNESS ALAN LATIES CAREER DEVELOPMENT PROGRAM [CF-CL-0416-0696-UCL]
- Health Labour Sciences Research Grant
- Ministry of Health, Labour and Welfare [201711107A]
- Great Britain Sasakawa Foundation Butterfield Awards
- Fight for Sight (UK) early career investigator award
- NIHR-BRC at Moorfields Eye Hospital
- UCL Institute of Ophthalmology
- NIHR-BRC at Great Ormond Street Hospital
- UCLInstitute of Child Health
- Great Britain Sasakawa Foundation Butterfield Award, UK
- Tsubota Laboratory, Inc
- Fuji Xerox Co., Ltd
- Kirin Company, Ltd
- Kowa Company, Ltd
- Novartis Pharmaceuticals
- Santen Pharmaceutical Co. Ltd
- ROHTO Pharmaceutical Co.,Ltd.
- Japan Agency for Medical Research and Development (AMED) [18ek0109282h0002]
- AMED
- Ministry of Health, Labor and Welfare, Japan [18ek0109282h0002]
- National Hospital Organization Network Research Fund, Japan [H30-NHO-Sensory Organs03]
- Novartis Research Grant (2018)
- [H26-26462674]
- Grants-in-Aid for Scientific Research [18K16943] Funding Source: KAKEN
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Purpose: To determine the clinical and genetic characteristics of patients with GUCY2D-associated retinal disorder (GUCY2D-RD). Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measurement, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR]). Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal fundus (40.0%). There were 11 patients with generalized cone-rod dysfunction (78.6%), two with entire functional loss (14.3%), and one with confined macular dysfunction (7.1%). There were nine families with ADCORD, one with ARCORD, one with ADMD, and one with ARLCA. Ten GUCY2D variants were identified, including four novel variants (p.Val56GlyfsTer262, p.Met246lle, p.Arg761Trp, p.Glu874Lys). Conclusions: This large cohort study delineates the disease spectrum of GUCY2D-RD. Diverse clinical presentations with various severities of ADCORD and the early-onset severe phenotype of ARLCA are illustrated. A relatively lower prevalence of GUCY2D-RD for ADCORD and ARLCA in the Japanese population was revealed. Translational Relevance: The obtained data help to monitor and counsel patients, especially in East Asia, as well as to design future therapeutic approaches.
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