Document Type
Journal Article
Publication Title
Investigative Ophthalmology and Visual Science
Volume
65
Issue
5
PubMed ID
38743414
Publisher
Association for Research in Vision and Ophthalmology
School
School of Science
RAS ID
70123
Funders
Western Australian Future Health and Innovation Fund, Government of Western Australia
McCusker Charitable Foundation (GNT1188694, GNT1054712, GNT1116360, MRF1142962)
Foundation Fighting Blindness
National Health and Medical Research Council
Nixon Visions Foundation (GNT1195713)
Grant Number
NHMRC Numbers : APP1116360, APP1099165, APP1109056
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.
DOI
10.1167/iovs.65.5.22
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Jeffery, R. C. H., Thompson, J. A., Lo, J., Chelva, E. S., Armstrong, S., Pulido, J. S., ... & Chen, F. K. (2024). Retinal dystrophies associated with peripherin-2: Genetic spectrum and novel clinical observations in 241 patients. Investigative Ophthalmology & Visual Science, 65(5), 22-22. https://doi.org/10.1167/iovs.65.5.22