Document Type
Article
Publication Date
5-1-2024
Abstract
PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.
METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations.
RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability.
CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.
Recommended Citation
Heath Jeffery, Rachael C.; Thompson, Jennifer A.; Lo, Johnny; Chelva, Enid S.; Armstrong, Sean; Pulido, Jose S.; Procopio, Rebecca; Vincent, Andrea L.; Bianco, Lorenzo; Battaglia Parodi, Maurizio; Ziccardi, Lucia; Antonelli, Giulio; Barbano, Lucilla; Marques, João P.; Geada, Sara; Carvalho, Ana L.; Tang, Wei C.; Chan, Choi M.; Boon, Camiel J. F.; Hensman, Jonathan; Chen, Ta-Ching; Lin, Chien-Yu; Chen, Pei-Lung; Vincent, Ajoy; Tumber, Anupreet; Heon, Elise; Grigg, John R.; Jamieson, Robyn V.; Cornish, Elisa E.; Nash, Benjamin M.; Borooah, Shyamanga; Ayton, Lauren N.; Britten-Jones, Alexis Ceecee; Edwards, Thomas L.; Ruddle, Jonathan B.; Sharma, Abhishek; Porter, Rowan G.; Lamey, Tina M.; McLaren, Terri L.; McLenachan, Samuel; Roshandel, Danial; and Chen, Fred K., "Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients" (2024). Wills Eye Hospital Papers. Paper 218.
https://jdc.jefferson.edu/willsfp/218
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Supplementary Material S2.pdf (553 kB)
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PubMed ID
38743414
Language
English
Comments
This article is the author's final published version in Investigative Ophthalmology & Visual Science, Volume 65, Issue 5, May 2024, Article number 22.
The published version is available at https://doi.org/10.1167/iovs.65.5.22.
Copyright © 2024 The Authors