# Nasal Retinal Degeneration Is a Feature of a Subset of CRX-Associated Retinopathies

## TL;DR

This study finds that nasal retinal degeneration is a common feature in some retinal diseases caused by mutations in the CRX gene.

## Contribution

The paper identifies nasal retinal degeneration as a novel feature of CRX-associated retinopathies.

## Key findings

- Nasal retinal degeneration was observed in 53.3% of patients with CRX-associated retinopathy.
- Nasal degeneration was more common in patients with maculopathy/cone-rod dystrophy and Leber congenital amaurosis.
- Genetic variants in the homeobox motif and activation domain were associated with nasal degeneration.

## Abstract

Background/Objectives: Genetic variants in the cone–rod homeobox (CRX) gene, a transcription factor critical for the differentiation, function, and survival of photoreceptors, are a rare cause of inherited retinal diseases (IRDs). CRX-associated retinopathies can produce variable phenotypes, including Leber congenital amaurosis (LCA), maculopathy (M), cone-rod dystrophy (CRD), and rod-cone dystrophy (RCD), such as retinitis pigmentosa (RP). Based on clinical observations at our eye institute, we hypothesized that nasal retinal degeneration is a feature of CRX-associated maculopathy and M/CRD. Methods: We performed an IRB-approved, retrospective review of patients at our eye institute with CRX-associated retinopathy to assess the frequency of nasal degeneration and potential genotype–phenotype correlations. Results: A total of 15 patients with a CRX-associated retinopathy and meeting the inclusion criteria were identified (LCA 3, RCD/RP 2, M/CRD 10). Overall, nasal degeneration occurred in 8 of 15 patients (53.3%) in the cohort. Nasal retinal degeneration was seen in the M/CRD (6 of 10; 60.0%) as well as LCA groups (2 of 3; 66.6%). No significant differences in age, gender, or presenting visual acuity were observed between patients with and without nasal degeneration. Genetic variants associated with nasal degeneration are localized to both the homeobox motif and activation domain. Intronic variants were relatively more common in patients with nasal degeneration, while missense variants predominated in those without, although these differences were not statistically significant. Conclusions: We conclude that nasal degeneration is a feature of a subset of CRX-associated phenotypes, affects both genders, and can be caused by genetic variants in multiple locations and of various subtypes.