RPE65 Variant p.(E519K) Causes a Novel Dominant Adult-Onset Maculopathy in 83 Affected Individuals.

ABSTRACT:

Purpose

Recessive RPE65-associated retinopathy is a well-known target for gene therapy, whereas dominant RPE65-associated retinopathy, due to the Irish founder variant p.(D477G), has been reported only once until now and is very rare. Here, we present the discovery of a novel, second dominant RPE65-associated retinopathy caused by variant c.1555G>A, p.(E519K).

Methods

Genomic data was investigated in a Belgian discovery cohort (n = 2873) and an international replication cohort (n = 18,796) with inherited retinal disease (IRD). Heterozygous p.(E519K) individuals underwent extensive phenotyping. Haplotype phasing was based on long-read sequencing and microsatellite analysis. Variant p.(E519K) was assessed in vitro using an enzymatic assay, Western blotting, co-immunoprecipitat

SUBMITTER: Van Vooren E 

PROVIDER: S-EPMC12468096 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature