期刊
EXPERIMENTAL EYE RESEARCH
卷 212, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2021.108761
关键词
Inherited retinal dystrophy; Leber congenital amaurosis; Early-onset retinitis pigmentosa; RPE65; Pathogenic variant; Genotype-phenotype correlation
资金
- Institute of Health Carlos III (ISCIII) of the Spanish Ministry of Health
- Center for Biomedical Research Network on Rare Diseases (CIBERER) [06/07/0036]
- IIS-FJD BioBank [PT13/0010/0012]
- FIS [PI16/00425, PI19/0321]
- RARE Genomics CM (CAM) [B2017/BMD-3721]
- European Regional Development Foundation (FEDER)
- Spanish National Organization of the Blind (ONCE)
- Ramon Areces Foundation
- Conchita Rabago Foundation
- University Chair UAM-IIS-FJD of Genomic Medicine
- IIS-Fundacion Jimenez Diaz-UAM Genomic Medicine Chair
- Autonomous Community of Madrid (CAM) [PEJD-2018/BMD-9544]
- Institute of Health Carlos III (ISCIII) [FI17/00192]
- Miguel Servet program from ISCIII [CPII17/00006]
This study found an association between the type of RPE65 variant carried and age at onset of the disease, with patients carrying different types of variants experiencing disease onset at different times. These findings provide useful data for understanding the phenotypes of RPE65-associated IRD.
Introduction: Biallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals progress to severe disease, with 50% of patients becoming legally blind by 20 years of age. Deeper knowledge of the mutational spectrum and the phenotype-genotype correlation in RPE65-related IRD is needed. Patients and methods: Forty-five affected subjects from 27 unrelated families with a clinical diagnosis of RPE65related IRD were included. Clinical evaluation consisted of self-reported ophthalmological history and objective ophthalmological examination. Patients' genotype was classified according to variant class (truncating or missense) or to variant location at different protein domains. The main phenotypic outcome measure was age at onset (AAO) of symptomatic disease and a Kaplan-Meier analysis of disease symptom event-free survival was performed. Results: Twenty-nine different RPE65 variants were identified in our cohort, 7 of them novel. Patients carrying two missense alleles showed a later disease onset than those with 1 or 2 truncating variants (log-rank test p <0.05). While 60% of patients carrying a missense/missense genotype presented symptoms before or during the first year of life, almost all patients with at least 1 truncating allele (91%) had an AAO <= 1 year (p <0.05). Conclusion: Our findings suggest an association between the type of RPE65 variant carried and AAO. These findings provide useful data on RPE65-associated IRD phenotypes and may help improve clinical and therapeutic management of these patients.
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