Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.
Journal
Investigative ophthalmology & visual science
Journal Volume
65
Journal Issue
5
Start Page
22
ISSN
1552-5783
Date Issued
2024-05-01
Author(s)
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
Lin, Chien-Yu
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
Chen, Fred K
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.
SDGs
Type
journal article