Genotype-Phenotype Associations for Cone-Rod Homeobox-linked Retinopathies

Abstract

Purpose : The Cone-Rod-Homeobox protein regulates rod/cone expression and is essential for the development of both cell types. It is unclear how individual CRX mutations alter human retinal morphology & visual function. We evaluated the association between phenotype severity & positioning of CRX truncation mutations in retinopathy patients.

Methods : Patients with known CRX mutations underwent genetic testing & comprehensive retinal phenotyping, including symptomatology, visual acuity, fundus AF, OCT, & ffERG. To assess how mutations affect CRX regulatory function, we performed pRho-reporter assays in mouse retinal explants.

Results : 28 CRX truncation mutations were identified, each causing a dominant retinopathy with reduced peripheral/central vision. Mutations earlier in the CRX protein appeared to produce a more severe phenotype compared to late truncations. pRho-reporter assays confirmed the impact of such mutations on CRX function.

Conclusions : This study broadens the currently known clinical presentations of CRX retinopathy, which depend on mutation type & position. Additional sample analysis will establish this genotype-phenotype correlation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.