Daich Varela, Malena;
Romo-Aguas, Juan Carlo;
Guarascio, Rosellina;
Ziaka, Kalliopi;
Aguila, Monica;
Hau, Kwan-Leong;
Li, Yumei;
... Michaelides, Michel; + view all
(2025)
RHO-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model – In Preparation for Clinical Trials.
Investigative Ophthalmology Visual Science
, 66
(9)
, Article 69. 10.1167/iovs.66.9.69.
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Abstract
Purpose: The purpose of this study was to describe the largest cohort of RHO-associated retinitis pigmentosa (RP) to date, analyzing the spectrum of phenotypes, variants, disease natural history, and genotype-phenotype correlations. / / Methods: Variants were classified using functional assays, animal models, and published data. Clinical assessments involved visual acuity (LogMAR), dilated fundus examinations, multimodal imaging (spectral-domain optical coherence tomography [SD-OCT] and fundus autofluorescence [FAF]), and international-standard electrophysiology. Cases were described as having generalized RP or sector RP according to fundus examination and imaging data. Longitudinal analysis evaluated progression rates of visual and structural parameters. / / Results: Two hundred patients (140 families) with likely disease-causing variants in RHO were identified. Positive family history was documented in 78.5% of the cases. Generalized RP was diagnosed in 64%, sector RP in 34.5%, and 1.5% were asymptomatic carriers. Fifty-six variants were identified, 54% were classified as class 2, 14% as class 1, 5% as class 4, and 2% as class 3. Variants in class 1 were associated with earlier symptom onset (mean = 13.5 years), generalized RP, and the worst baseline visual acuity (mean LogMAR = 0.45). Pro347Leu was the most prevalent variant (17%). Longitudinal analysis showed slower progression in sector RP (0.01 LogMAR/year) compared to generalized RP (0.03 LogMAR/year). Imaging revealed distinct phenotypes, including choroideremia-like features in generalized RP and inferior retinal involvement in sector RP that an animal model suggests is light related. / / Conclusions: RHO-associated RP encompasses a wide phenotypic spectrum with distinct genetic subtypes influencing disease severity and progression. These findings provide critical insights for patient counseling, identifying clinical endpoints, participant stratification, and guiding therapeutic development.
| Type: | Article |
|---|---|
| Title: | RHO-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model – In Preparation for Clinical Trials |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1167/iovs.66.9.69 |
| Publisher version: | https://doi.org/10.1167/iovs.66.9.69 |
| Language: | English |
| Additional information: | © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | rhodopsin, inherited retinal dystrophies (IRDs), genetic diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212308 |
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