Purchase this article with an account.
Kaylie D. Webb, Hemaxi M. Patel, Sara J. Bowne, Lori S. Sullivan, Abigail T. Fahim, Stephen P. Daiger, Dennis R. Hoffman, David G. Birch, Dianna K. Wheaton; Assessment of Phenotypic Variability Among Female Carriers of X-linked Retinitis Pigmentosa (xlRP) due to RPGR Mutations. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4981.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
X-linked retinitis pigmentosa (xlRP) can lead to strikingly different clinical outcomes, even among individuals within a family. Phenotypes in female carriers range from undetectable to mild symptoms, to early onset, severe vision loss. This study documents the clinical consequence and disease severity in carriers of confirmed GTPase regulator (RPGR) mutations.
Sixty carriers with confirmed RPGR mutations ranging in age from 11 to 66 yrs (mean=42 yrs) were recruited for genetic analysis and clinical examination on both eyes including: best-corrected visual acuity (VA), Humphrey visual fields (HVF), dark-adapted thresholds (DA), full-field (ffERG) and multi-focal electroretinography (mfERG), frequency domain optical coherence tomography (fdOCT), and fundus photography. Subjects with ffERG cone amplitude responses greater than 35 µV in the worst eye were categorized as mildly affected (n=30), moderately affected (n=17) had responses between 10 and 35 µV, while severely affected (n=13) had responses < 10 µV.
Mean (± SD) age of the mild and moderate groups was 41±12 yrs, and severely affected carriers was 50±12 yrs. There was no statistical significant difference in ages across the three groups (p=0.067). Percent of mutations predicted to result in nonsense-mediated decay (NMD) vs. mutations predicted to result in a translated, abnormal protein product (APP) were identified: (mild: 30% NMD; 70% APP, moderate: 46% NMD; 54% APP, severe: 53% NMD; 47% APP). The logMAR VA for the mild group was 0.1±0.3, 0.3±0.4 for moderate, and 0.6±0.5 for severe. HVF size was 49±9.2 degrees (mild), 28±20.4 degrees (moderate) and 7±15.0 degrees (severe). DA thresholds were elevated an average of 1.7±0.3 log units (mild), 2.2±1.1 log units (moderate), and 3.8±1.4 log units (severe). MfERG responses ranged from normal to below lower limit of normal in amplitude. FdOCT scans ranged from unremarkable to significant changes in the photoreceptor layer. Fundus photography showed no defects to severe peripheral pigmentary degeneration.
Heterogeneity was considerable in this group of carriers. Theories to explain phenotypic diversity include differences in disease-causing mutations, genetic background, or environmental factors. This project should substantially expand our understanding of the varied clinical consequences of RPGR mutations causing xlRP in females.
This PDF is available to Subscribers Only