LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS.
Adolescent
Adult
Child
Child, Preschool
Electroretinography
Female
Genetic Association Studies
Genotype
Humans
Infant
Infant, Newborn
Longitudinal Studies
Male
Middle Aged
Mutation
Retina
/ physiopathology
Retinal Degeneration
/ diagnostic imaging
Retrospective Studies
Tomography, Optical Coherence
Visual Acuity
/ physiology
Visual Fields
/ physiology
Young Adult
cis-trans-Isomerases
/ genetics
Journal
Retina (Philadelphia, Pa.)
ISSN: 1539-2864
Titre abrégé: Retina
Pays: United States
ID NLM: 8309919
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
pubmed:
8
2
2020
medline:
6
7
2021
entrez:
8
2
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32032261
doi: 10.1097/IAE.0000000000002681
pii: 00006982-202009000-00020
doi:
Substances chimiques
retinoid isomerohydrolase
EC 3.1.1.64
cis-trans-Isomerases
EC 5.2.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1812-1828Références
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