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Publication year
2020Source
Retina-The Journal of Retinal and Vitreous Diseases, 40, 9, (2020), pp. 1812-1828ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Ophthalmology
Journal title
Retina-The Journal of Retinal and Vitreous Diseases
Volume
vol. 40
Issue
iss. 9
Page start
p. 1812
Page end
p. 1828
Subject
Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience; Cognitive Neuroscience - Radboud University Medical Center; Ophthalmology - Radboud University Medical CenterAbstract
PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes.
This item appears in the following Collection(s)
- Academic publications [244084]
- Electronic publications [131085]
- Faculty of Medical Sciences [92872]
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