Bellingrath, Julia-Sophia and Ochakovski, G. Alex and Seitz, Immanuel P. and Kohl, Susanne and Zrenner, Eberhart and Hanig, Nicola and Prokisch, Holger and Weber, Bernhard H. and Downes, Susan M. and Ramsden, Simon and MacLaren, Robert E. and Fischer, M. Dominik (2017) High Symmetry of Visual Acuity and Visual Fields in RPGR-Linked Retinitis Pigmentosa. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 58 (11). pp. 4457-4466. ISSN 0146-0404, 1552-5783
Full text not available from this repository. (Request a copy)Abstract
PURPOSE. Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause 70% to 90% of X-linked retinitis pigmentosa (XLRP3) cases, making this gene a high-yield target for gene therapy. This study analyzed the utility of relevant clinical biomarkers to assess symmetry and rate of progression in XLRP3. METHODS. A retrospective, cross-sectional analysis of 50 XLRP3 patients extracted clinical data including visual acuity (VA), visual fields (I4e and III4e targets), foveal thickness, and ERG data points alongside molecular genetic data. Symmetry was assessed by using linear regression analysis. Kaplan-Meier survival curves (KMCs) and generalized linear mixed model calculations were used to describe disease progression. RESULTS. Ninety-six percent of patients exhibited a rod-cone phenotype, and 4% a cone-rod phenotype. Open reading frame 15 (ORF15) was confirmed as a mutational hotspot within RPGR harboring 73% of exonic mutations. Significant variability, but no clear genotype-phenotype relationship, could be shown between mutations located in exons 1-14 versus ORF15. All biomarkers suggested a high degree of symmetry between eyes but demonstrated different estimates of disease progression. VA and foveal thickness, followed by perimetry III4e, were the most useful endpoints to evaluate progression. KMC estimates predicted a loss of 6/6 vision at a mean of 34 years (+/- 2.9; 95% confidence interval). CONCLUSIONS. XLRP3 affects retinal structure and function symmetrically, supporting the use of the fellow eye as an internal control in interventional trials. VA and kinetic visual fields (III4e) seem promising functional outcome measures to assess disease progression. KMC analysis predicted the most severe decline in vision between the third and fourth decade of life.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPTICAL COHERENCE TOMOGRAPHY; NUCLEOTIDE-EXCHANGE FACTOR; GENE-THERAPY; MUTATION ANALYSIS; PHOTORECEPTOR DEGENERATION; EXON ORF15; IDENTIFICATION; FAMILIES; ISOFORMS; DISEASE; retinitis pigmentosa; retinitis pigmentosa GTPase regulator (RPGR); gene therapy; disease progression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:15 |
| Last Modified: | 28 Feb 2019 11:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1285 |
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