RHO-Associated Retinitis Pigmentosa: Genetics, Phenotype, Natural History, Functional Assays, and Animal Model – In Preparation for Clinical Trials

作者：Malena Daich Varela, J. Romo-Aguas, Rosellina Guarascio, Kalliopi Ziaka, Monica Aguila, Kwan Hau, Yumei Li, Rui Chen, A. Kalitzeos, A. Robson, Rebecca A. Baker, O. Mahroo, A. Webster, H. Chan, N. Lubock, Matthew L. Albert, Michael E. Cheetham, M. Michaelides · 发表于：Investigative Ophthalmology and Visual Science · 年份：2025 · DOI：10.1167/iovs.66.9.69 · 被引用次数：10 · 研究领域：Medicine

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 p...