Retinosis pigmentaria autosómica dominante: informe de una familia extensa con la variante Asp-190-Tyr

Abstract

Introduction and objectives

Retinitis pigmentosa (RP) represents a spectrum of rod-cone inherited disorders with characteristic symptoms, and functional changes. The Asp-190-Tyr pathogenic variant of the RHO gene impairs rodopsin transport through the endoplasmic reticulum, leading to accumulation within photoreceptors, inducing cytotoxicity. This report presents the ophthalmologic phenotype of this rare variant.

Materials and Methods

Retrospective study including patients from one extended family presenting with RP, with an autosomal dominant variant of the RHO gene (Asp-190-tyr). Baseline demographic/ophthalmologic data and ancillary testing was collected.

Results

Twelve individuals were included; eight had generalized RP. The mean age was 64 years - four were female. Genetic testing in 5/8 patients with RP revealed an autosomal dominant variant in the RHO gene, with replacement of an aspartic acid with tyrosine at codon 190. Visual acuity ranged from no light perception to 6/10. Fundoscopy and fundus autofluorescence showed bilateral generalized RP pattern: optic disc pallor, bone spicules, and arterial narrowing. Perimetry in four patients showed tunnel vision. Electrophysiology revealed marked wave reduction in both pattern and flash ERG. Severe atrophy of the outer retinal layers with cystoid macular oedema was observed in 4/8 patients.

Conclusions

This study highlights the phenotype of the Asp-190-Tyr variant. Previously, it was described in a family with a regional pattern of RP and relatively preserved visual function. Our study changes this paradigm, with patients presenting with a generalized RP phenotype and significant visual impairment. The provided data may help offer accurate prognostic information to patients with this variant.