# Phenotypic characterization of a female patient with retinitis pigmentosa caused by a homozygous X-linked RPGRORF15 mutation

## TL;DR

A female patient with a rare X-linked mutation causing retinitis pigmentosa is described, showing severe retinal degeneration similar to affected males.

## Contribution

The paper presents a novel clinical case of a homozygous RPGRORF15 mutation in a female patient with RP.

## Key findings

- The patient exhibited severe retinal degeneration with global photoreceptor loss and decreased FAF signal.
- The patient's phenotype was similar to that of her affected uncle, including central photoreceptor residuals and patchy FAF patterns.
- The patient's homozygous RPGRORF15 mutation suggests potential eligibility for future therapeutic trials.

## Abstract

To describe a detailed phenotypic expression of a homozygous female with retinitis pigmentosa (RP) within a consanguineous family revealing an extremely rare genetic constellation with possible implications for future emerging therapies in addressing inherited retinal dystrophies.

Multimodal retinal imaging including wide field fundus photography, fundus autofluoresence (FAF), high-resolution spectral domain optical coherence tomography (SD-OCT) imaging, functional testing comprising visual fields and electroretinogram as well as genetic testing were performed in two consanguine cases of RP.

A 44-year-old female patient was referred for evaluation and counseling for potential treatment options presenting with night blindness and visual field defects since early childhood. Extended ophthalmologic examination including multimodal retinal imaging and functional testing showed a clinical presentation of a RP phenotype. The accompanying 50-year-old paternal uncle reported similar visual symptoms and was diagnosed with RP during adolescence. In multimodal retinal imaging, both patients presented a similar phenotype and comparable disease severity with a global photoreceptor loss and decreased FAF signal. In the uncle, there was evidence for central residuals of the photoreceptor band on SD-OCT imaging and a patchy FAF pattern. Genetic testing revealed a rare constellation of a homozygous RP GTPase Regulator protein (RPGRORF15) mutation in the female patient.

This detailed phenotype-genotype correlation presents a novel clinical presentation of a rare homozygous RPGRORF15 mutation in a female patient that exhibits severe retinal degeneration similar to affected males and therefore, considering they don't have a wildtype allele, may be suitable for inclusion in upcoming therapeutic treatment trials.