{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:22:23Z","timestamp":1792167743412,"version":"4.4.0"},"reference-count":93,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Thames Valley"},{"name":"South Midlands Clinical Research Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Purpose: To investigate genotype\u2013phenotype correlations in PRPH2-retinopathies in a cohort of 36 patients from the Oxford Eye Hospital and report on novel pathogenic variants. Methods: Clinical data, including best corrected visual acuities (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) imaging, were analysed. Genetic testing was performed using next-generation sequencing (NGS). Results: In this cohort, 26 different PRPH2 variants, including 8 novel variants, were identified. Variants were clustered in the D2 loop of the protein. A diverse range of phenotypes were observed: pseudo-Stargardt pattern dystrophy (PSPD) (47.2%), adult-onset vitelliform macular dystrophy (AVMD) (22.2%), pattern dystrophy (PD) (25.0%), atypical macular dystrophy (2.8%), and retinitis pigmentosa (RP) (2.8%). The mean age of symptom onset was 44.0 \u00b1 14.4 years. Mean BCVA was 0.20 \u00b1 0.54 logMAR OD and 0.14 \u00b1 0.29 logMAR OS at baseline and 0.33 \u00b1 0.40 logMAR OD and 0.32 \u00b1 0.40 logMAR OS after a mean follow up duration of 6.0 \u00b1 3.2 years (range 1\u201311 years). A thickened ellipsoid zone (EZ) was noted in 34\/36 patients with a mean EZ thickness of 44.3 \u00b1 11.3 \u00b5m OD and 42.7 \u00b1 11.6 \u00b5m OS. No clear genotype\u2013phenotype correlations were observed. Conclusions: The significant phenotypic range described in this study is consistent with the previously reported phenotypic variability in PRPH2 retinopathy and emphasises the complexity of establishing genotype\u2013phenotype correlations in this disease. The thickness of the EZ on OCT may serve as a useful biomarker in distinguishing PRPH2 retinopathy from other phenocopies. These findings contribute to improved understanding of PRPH2 retinopathy and help inform diagnosis and genetic counselling.<\/jats:p>","DOI":"10.3390\/genes16091016","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:49:34Z","timestamp":1756309774000},"page":"1016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genotype\u2013Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-3202","authenticated-orcid":false,"given":"Saoud","family":"Al-Khuzaei","sequence":"first","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"},{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7496-6121","authenticated-orcid":false,"given":"Mital","family":"Shah","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"},{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Reginald","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Baba","sequence":"additional","affiliation":[{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morag","family":"Shanks","sequence":"additional","affiliation":[{"name":"Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"},{"name":"Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Clouston","sequence":"additional","affiliation":[{"name":"Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK"},{"name":"Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"MacLaren","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"},{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Halford","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4455-2814","authenticated-orcid":false,"given":"Samantha R.","family":"De Silva","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"},{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-2665","authenticated-orcid":false,"given":"Susan M.","family":"Downes","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"},{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.preteyeres.2017.03.003","article-title":"Unravelling the genetics of inherited retinal dystrophies: Past, present and future","volume":"59","author":"Broadgate","year":"2017","journal-title":"Prog. 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