Premium
RPE 65 mutation frequency and phenotypic variation according to exome sequencing in a tertiary centre for genetic eye diseases in China
Author(s) -
Li Shiqiang,
Xiao Xueshan,
Yi Zhen,
Sun Wenmin,
Wang Panfeng,
Zhang Qingjiong
Publication year - 2020
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.14181
Subject(s) - rpe65 , missense mutation , exome sequencing , genetics , proband , phenotype , biology , compound heterozygosity , mutation , exome , retinal degeneration , gene , genetic enhancement
Purpose Retinoid isomerohydrolase RPE 65 has received a tremendous amount of attention due to successful clinical gene therapy for Leber congenital amaurosis ( LCA ) cases caused by RPE 65 mutations. This study aimed to evaluate the frequency of RPE 65 mutations and the associated phenotypes based on exome sequencing. Methods RPE 65 variants were collected from exome sequencing data obtained from 2133 probands with different forms of hereditary retinal degeneration ( HRD ). Clinical data were collected from probands with homozygous or compound heterozygous variants in RPE 65 . Associated phenotypes were characterized based on clinical data. Results Biallelic RPE 65 mutations were detected in 18 families, including eight with LCA , five with early‐onset retinal degeneration, four with fundus albipunctatus‐like ( FA ‐like) changes and one with high hyperopia. These cases accounted for approximately 3.0% (8/269) of LCA and 0.8% (18/2133) of HRD cases. An almost identical FA ‐like change was identified in seven patients from four unrelated families with RPE 65 mutations. Classification of mutations suggested that FA ‐like changes may be associated with biallelic missense mutations in RPE 65 . Conclusion Fundus albipunctatus‐like (FA‐like) change, a common characteristic fundus sign in RPE 65 biallelic mutations, was unexpected but was confirmed by the finding that affected siblings from different families exhibited similar phenotypes. These results enrich our understanding of RPE 65 mutation frequencies and their associated phenotypic variants.