Document Type
Journal Article
Publication Title
Genes
Volume
12
Issue
12
Publisher
MDPI
School
School of Science
RAS ID
40583
Funders
National Health and Medical Research Council
Macular Disease Foundation Australia
McCusker Charitable Foundation
Miocevich Retina Fellowship
Retina Australia
Grant Number
NHMRC Number : GNT1116360, GNT1188694, GNT1054712, MRF1142962
Grant Link
http://purl.org/au-research/grants/nhmrc/GNT1116360
Abstract
Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed bial-lelic ABCA4 mutations from five genotype groups: c.6079C > T, c.[2588G > C;5603A > T], c.3113C > T, c.5882G > A and c.5603A > T. Fundus autofluorescence (AF) 30◦ × 30◦ images were manually seg-mented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF formation and symptom onset was compared. A total of 75 eyes from 39 STGD1 patients (17 male [44%]; mean ± SD age 45 ± 19 years; range 21–86) were recruited. Patients with c.3113C > T or c.6079C > T had a significantly faster effective radius GR at 0.17 mm/year (95% CI 0.12 to 0.22; p < 0.001 and 0.14 to 0.21; p < 0.001) respectively, as compared to those patients harbouring c.5882G > A at 0.06 mm/year (95% CI 0.03–0.09), respectively. Future clinical trial design should consider the effect of genotype on the effective radius GR and the timing of DDAF formation relative to symptom onset.
DOI
10.3390/genes12121981
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Life Sciences Commons, Medicine and Health Sciences Commons, Physical Sciences and Mathematics Commons
Comments
Heath Jeffery, R. C., Thompson, J. A., Lo, J., Lamey, T. M., McLaren, T. L., McAllister, I. L., . . . Chen, F. K. (2021). Genotype-specific lesion growth rates in stargardt disease. Genes, 12(12), article 1981.
https://doi.org/10.3390/genes12121981