Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

Al-Khuzaei, Saoud; Shah, Mital; Reginald, Arun; Baba, Edna; Shanks, Morag; Clouston, Penny; MacLaren, Robert E.; Halford, Stephanie; De Silva, Samantha R.; Downes, Susan M.

doi:10.3390/genes16091016

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Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

by

Saoud Al-Khuzaei

^1,2

,

Mital Shah

^1,2

,

Arun Reginald

³,

Edna Baba

²,

Morag Shanks

^4,5,

Penny Clouston

^4,5,

Robert E. MacLaren

^1,2,

Stephanie Halford

¹,

Samantha R. De Silva

^1,2

and

Susan M. Downes

^1,2,*

¹

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK

²

Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK

³

The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada

⁴

Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK

⁵

Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK

^*

Author to whom correspondence should be addressed.

Genes 2025, 16(9), 1016; https://doi.org/10.3390/genes16091016

Submission received: 31 July 2025 / Revised: 18 August 2025 / Accepted: 22 August 2025 / Published: 27 August 2025

(This article belongs to the Section Human Genomics and Genetic Diseases)

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Abstract

Purpose: To investigate genotype–phenotype 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 ± 14.4 years. Mean BCVA was 0.20 ± 0.54 logMAR OD and 0.14 ± 0.29 logMAR OS at baseline and 0.33 ± 0.40 logMAR OD and 0.32 ± 0.40 logMAR OS after a mean follow up duration of 6.0 ± 3.2 years (range 1–11 years). A thickened ellipsoid zone (EZ) was noted in 34/36 patients with a mean EZ thickness of 44.3 ± 11.3 µm OD and 42.7 ± 11.6 µm OS. No clear genotype–phenotype 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–phenotype 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.

Keywords: PRPH2; pattern dystrophy; genetics; inherited; OCT; fundus autofluorescencec

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MDPI and ACS Style

Al-Khuzaei, S.; Shah, M.; Reginald, A.; Baba, E.; Shanks, M.; Clouston, P.; MacLaren, R.E.; Halford, S.; De Silva, S.R.; Downes, S.M. Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK. Genes 2025, 16, 1016. https://doi.org/10.3390/genes16091016

AMA Style

Al-Khuzaei S, Shah M, Reginald A, Baba E, Shanks M, Clouston P, MacLaren RE, Halford S, De Silva SR, Downes SM. Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK. Genes. 2025; 16(9):1016. https://doi.org/10.3390/genes16091016

Chicago/Turabian Style

Al-Khuzaei, Saoud, Mital Shah, Arun Reginald, Edna Baba, Morag Shanks, Penny Clouston, Robert E. MacLaren, Stephanie Halford, Samantha R. De Silva, and Susan M. Downes. 2025. "Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK" Genes 16, no. 9: 1016. https://doi.org/10.3390/genes16091016

APA Style

Al-Khuzaei, S., Shah, M., Reginald, A., Baba, E., Shanks, M., Clouston, P., MacLaren, R. E., Halford, S., De Silva, S. R., & Downes, S. M. (2025). Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK. Genes, 16(9), 1016. https://doi.org/10.3390/genes16091016

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Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

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