Impaired glutamylation of RPGR^ORF15 underlies the cone-dominated phenotype associated with truncating distal ORF15 variants.

ABSTRACT: Pathogenic variants in the Retinitis pigmentosa GTPase regulator (RPGR) gene lead to a clinically severe form of X-linked retinal dystrophy. However, it remains unclear why some variants cause a predominant rod, while others result in a cone-dominated phenotype. Post-translational glutamylation of the photoreceptor-specific RPGR^ORF15 isoform by the TTLL5 enzyme is essential for its optimal function in photoreceptors, and loss of TTLL5 leads to retinal dystrophy with a cone phenotype. Here we show that RPGR retinal disease, studied in a single cohort of 116 male patients, leads to a clear progressive shift from rod- to cone-dominating phenotype as the RPGR^ORF15 variant location approaches the distal part of the Open Reading Frame 15 (ORF15) region. The rod photo

SUBMITTER: Cehajic-Kapetanovic J 

PROVIDER: S-EPMC9897430 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature