Higher throughput assays for understanding the pathogenicity of variants of unknown significance (VUS) in the RPE65 gene.

ABSTRACT:

Purpose

RPE65 is a key enzyme in the visual cycle that regenerates 11-cis retinal. Mutations in RPE65 cause a retinal dystrophy that is treatable with an FDA-approved gene therapy. Variants of unknown significance (VUS) on genetic testing can prevent patients from obtaining a firm genetic diagnosis and accessing gene therapy. Since most RPE65 mutations have a low protein expression level, this study developed and validated multiple methods for assessing the expression level of RPE65 variants. This functional evidence is expected to aid in reclassifying RPE65 VUS as pathogenic, which in turn can broaden the application of gene therapy for RPE65 patients.

Methods

30 different variants of RPE65 (12 pathogenic, 13 VUS, 5 benign) w

SUBMITTER: Pormehr LA 

PROVIDER: S-EPMC11838478 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature