March 2007
Volume 48, Issue 3
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Retina  |   March 2007
Disease Course of Patients with X-linked Retinitis Pigmentosa due to RPGR Gene Mutations
Author Affiliations
  • Michael A. Sandberg
    From the The Berman-Gund Laboratory for the Study of Retinal Degenerations and
  • Bernard Rosner
    From the The Berman-Gund Laboratory for the Study of Retinal Degenerations and
  • Carol Weigel-DiFranco
    From the The Berman-Gund Laboratory for the Study of Retinal Degenerations and
  • Thaddeus P. Dryja
    The Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
  • Eliot L. Berson
    From the The Berman-Gund Laboratory for the Study of Retinal Degenerations and
Investigative Ophthalmology & Visual Science March 2007, Vol.48, 1298-1304. doi:10.1167/iovs.06-0971
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      Michael A. Sandberg, Bernard Rosner, Carol Weigel-DiFranco, Thaddeus P. Dryja, Eliot L. Berson; Disease Course of Patients with X-linked Retinitis Pigmentosa due to RPGR Gene Mutations. Invest. Ophthalmol. Vis. Sci. 2007;48(3):1298-1304. doi: 10.1167/iovs.06-0971.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To measure the rates of visual acuity, visual field, and ERG loss in patients with X-linked retinitis pigmentosa due to RPGR mutations and to determine whether these rates differ from those of patients with dominant retinitis pigmentosa due to RHO mutations.

methods. Snellen visual acuities, Goldmann visual field areas (V4e white test light), and 30 Hz (cone) full-field ERG amplitudes were recorded for an average of 9.8 years in 113 patients with RPGR mutations. After censoring data to eliminate ceiling and floor effects, we used longitudinal regression to estimate mean rates of change and to compare these rates with those of a previously studied cohort of 134 patients with dominant retinitis pigmentosa due to RHO mutations, who were followed for an average of 8.9 years. Survival analysis was used to compare the age distribution of legal blindness in these two groups. To explain group differences in visual acuity, optical coherence tomograms were recorded in some patients to visualize central retinal structure.

results. Mean annual exponential rates of decline for the patients with RPGR mutations were 4.0% for visual acuity, 4.7% for visual field area, and 7.1% for ERG amplitude. Each of these rates was significantly different from zero (P < 0.001). The rates of visual acuity and visual field loss were significantly faster than the corresponding rates in the RHO patients (1.6%, P < 0.001 and 2.9%, P = 0.002, respectively), whereas the rate of ERG amplitude loss was comparable to that in the RHO patients (7.7%, P = 0.39). The median age of legal blindness was 32 years younger in the RPGR patients than in the RHO patients, due primarily to loss of visual acuity rather than to loss of visual field. Loss of acuity in RPGR patients appeared to be associated with foveal thinning.

conclusions. Patients with X-linked retinitis pigmentosa due to RPGR mutations lose visual acuity and visual field more rapidly than do patients with dominant retinitis pigmentosa due to RHO mutations.

In retinitis pigmentosa, it is commonly thought that the X-linked form progresses most rapidly and that the dominant form progresses least rapidly, but this impression is primarily based on single visits and not on observing the same patients over time. In 1985 a longitudinal study showed that patients with dominant retinitis pigmentosa as a group were half as likely to lose cone electroretinogram (ERG) amplitude over a 3-year time interval as were patients with autosomal recessive, X-linked, and isolated disease combined. 1 However, the number of patients was too small and the follow-up too short in that study to consider similar comparisons with respect to loss of visual acuity and visual field area, which progress more slowly than loss of ERG amplitude, or to compare the X-linked form with other genetic types. 
The discovery of the molecular bases for different forms of retinitis pigmentosa has allowed us and others to reclassify patients according to their responsible gene defects. We recently reported mean rates of decline in ocular function for a large cohort of patients with dominant retinitis pigmentosa due to mutations in the rhodopsin (RHO) gene. 2 In the present study we report mean rates of decline in a similar-sized cohort of patients with X-linked retinitis pigmentosa due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, the protein of which is expressed in the connecting cilia of cones as well as rods, 3 and compare these rates with those of patients with RHO mutations. 
Methods
Patients
This study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Boards of the Massachusetts Eye and Ear Infirmary and Harvard Medical School. We measured visual acuities, visual fields, and ERGs from 113 males (mean age at baseline: 26.1 years, age range at baseline, 5–61 years) with X-linked retinitis pigmentosa due to an RPGR mutation and at least 3 years of follow-up. The methods used to identify the RPGR mutations in these patients and the DNA sequences of the mutations have been reported. 4 5 The RPGR dataset was derived from the results of an average of 7.2 ocular examinations per patient performed from 1975 to 2005 with the same test conditions; follow-up ranged from 3 to 28 years with a mean of 9.8 years. The RHO dataset, derived from a previous study, 2 was also limited to patients with at least 3 years of follow-up. This yielded a sample of 134 patients (mean age at baseline: 36.0 years, age range at baseline: 8–66 years) who had been observed for 3 to 24 years, with an average follow-up of 8.9 years based on an average of 6.2 examinations per patient. The mean age at baseline of the patients with RPGR mutations was significantly younger than that of the patients with RHO mutations (P < 0.001). 
Clinical Evaluation
The patients with RPGR mutations and those with RHO mutations underwent identical ocular examinations. We recorded best corrected visual acuity by using a projected Snellen chart and coded them in decimal form (e.g., 20/40 = 0.5). Kinetic visual fields were measured to the V4e white test light and to one or more smaller test lights in the Goldmann perimeter against the standard background of 31.5 apostilbs, bringing the test light from nonseeing to seeing areas. Fields were plotted with a digitizing tablet or scanned by custom software and converted to areas in square degrees. Although a cartographic distortion arises from projecting the curved surface of the perimeter onto the flat visual field chart 6 and the projection of the visual field onto the retina is nonlinear based on a schematic eye, 7 most longitudinal studies of visual field progression in retinitis pigmentosa have not applied corrections to their chart data, 1 2 8 9 10 and we elected to do the same for consistency. We elicited full-field cone ERGs with 10-μs, 30-Hz flashes of white light (0.2 cd-s/m2) after pupillary dilation, 45 minutes of dark adaptation, and having recorded responses in the dark to 0.5 Hz flashes of light. ERGs were monitored with a contact lens electrode on the topically anesthetized cornea and differentially amplified. Consecutive responses to 30-Hz flashes greater than 10 μV in amplitude were photographed from the screen of an oscilloscope or digitized and quantified by computer. Smaller responses were digitized, smoothed with a band-pass filter, and averaged. Waveforms in response to 30-Hz flashes were quantified with respect to trough-to-peak amplitudes, and amplitudes <0.05 μV, considered nondetectable, were recoded as 0.05 μV. In this study, we limited our analyses to the V4e white test light for measuring visual fields and to 30-Hz white flashes for eliciting ERGs, because only these conditions of testing provided us with sufficiently large data sets to estimate rates of change with high precision. 
As part of a separate program, 11 we had recorded optical coherence tomograms (OCTs) from 5 of the patients with RPGR mutations (age range, 19–47 years) and from 10 of the patients with RHO mutations (age range, 20–52 years). The RPGR patients had visual acuities of 20/30 to 20/200, and the RHO patients had visual acuities of 20/20 to 20/60 (excluding an eye of one patient with a history of deep amblyopia). We evaluated these tomograms to search for a structural basis for visual acuity differences in these two groups. 
Statistical Analyses
For estimating mean rates of change, we censored visual acuities of 20/20, except those that followed a lower value, to minimize a ceiling effect, because on our coding sheet we had constrained Snellen visual acuities to be ≤20/20. To minimize floor effects, we also censored patients with baseline visual acuities <20/100 and follow-up data after visual acuity declined to <20/100. For patients who became aphakic or pseudophakic in either eye at follow-up, those follow-up visits were excluded from visual acuity analyses. We also censored baseline visual field areas <78 deg2 (i.e., equivalent to a diameter of 10°) and follow-up data after the first occurrence of an area <78 deg2 to minimize floor effects. To minimize floor effects, we censored baseline ERG amplitudes <0.68 μV and follow-up data after the amplitude decreased to <0.34 μV. The censoring criteria were those applied in a previous study of patients with dominant RHO mutations. 2 After applying these criteria, we eliminated patients from a given analysis if their residual follow-up was <3 years. 
We converted all measures of ocular function to natural logarithms, because an exponential model has been shown to be optimal for evaluating cell loss over time in animal models of retinitis pigmentosa, 12 provides a good fit for describing short-term disease progression in patients with retinitis pigmentosa, 2 and has been used in several longitudinal studies of retinitis pigmentosa. 1 2 8 9 10 13 14 Repeated-measures longitudinal regression (performed with PROC MIXED of SAS, ver. 9; SAS Institute, Cary, NC) was used to estimate the mean rate of change for each outcome measure, based on the average loge value for both eyes at each visit (when data for both eyes were available). By including terms for genotype (i.e., RPGR versus RHO mutation) and the cross-product of time × genotype, we compared mean slopes in patients with RPGR mutations versus mean slopes in patients with RHO mutations. We also used longitudinal regression to compare the mean rates of progression in patients with RPGR mutations in exons 1 to 14 (n = 33) with the mean rates in patients who had RPGR mutations in open reading frame (ORF) 15 (n = 80), because a previous analysis had suggested differences in ocular function between these two groups based on single visits. 5  
We used the commercial software (PROC LIFEREG of SAS) to fit a Weibull function to survival data and compare the age distribution of legal blindness in patients with RPGR mutations to the corresponding distribution in patients with RHO mutations. These plots provide a visualization of the long-term course of disease, and the model allows inclusion of left-censored data (i.e., a patient failing at baseline) and right-censored data (i.e., a patient not failing during follow-up) as well as interval-censored data (i.e., a patient failing between exams occurring at ages x1 and x2). For this purpose, we applied failure criteria (i.e., a visual acuity ≤20/200 or a visual field area ≤314 deg2 in one eye and a visual acuity ≤20/200 or a visual field area ≤314 deg2 in the fellow eye) to the entire dataset. The area of 314 deg2 corresponds to an equivalent diameter of 20° (i.e., a criterion for legal blindness) and was used in lieu of measuring the linear extent of each remaining visual field directly from charts. We also used a visual acuity ≤20/200 alone and a visual field area ≤314 deg2 alone as failure criteria, to determine which was the critical factor that led to legal blindness in each group. 
Results
Baseline Ocular Function
Tables 1 and 2list the baseline raw data and mean values for the RPGR patients with mutations in exons 1 to 14 and with ORF15 mutations, respectively. None of the mean values in one group is significantly different from the corresponding mean value in the other group. 
Mean Rates of Change
Table 3shows the mean annual loge rates of change in the patients with RPGR mutations, with standard errors and significance levels. The mean loge values correspond to mean annual exponential rates of decline of 4.0% for Snellen visual acuity, 4.7% for visual field area to the V4e test light, and 7.1% for cone ERG amplitude to 30-Hz flashes. In comparison, the RHO patients had a mean annual exponential rate of visual acuity decline (1.6%) and a mean annual exponential rate of visual field decline (2.9%) that were slower than the corresponding rates in the patients with RPGR mutations (P < 0.001 and P = 0.002, respectively). In contrast, the RHO patients had a mean annual exponential rate of decline in ERG amplitude (7.7%) that was not significantly different from that of the RPGR patients (P = 0.39). 
When we divided our patients with RPGR mutations into those with mutations in exons 1 to 14 and those with mutations in ORF15, we found a significant group difference in the mean annual exponential rates of decline in ERG amplitude (9.5% versus 6.3%, respectively; P = 0.005), but no significant difference in the rates of decline in visual acuity (3.4% versus 4.3%, respectively; P = 0.17) or visual field (4.9% versus 4.6%, respectively; P = 0.78). 
Median Age to Reach Legal Blindness
We found a significant effect of genotype on the age distribution for legal blindness (P < 0.001). Figure 1shows that our patients with RPGR mutations reached legal blindness, based on loss of acuity and/or field, at a median age (45 years) that was 32 years younger than that of our patients with RHO mutations (77 years). Figure 2shows that the development of legal blindness was driven primarily by visual acuity loss in the patients with RPGR mutations and by visual field loss in the patients with RHO mutations. That is, in the patients with RPGR mutations, the survival curve based on a visual acuity of 20/200 or less is shifted to younger ages compared with the survival curve based on a visual field area of 314 deg2 or less. In contrast, the visual field survival curve is shifted to younger ages compared with the visual acuity survival curve of the patients with RHO mutations. 
Figure 2also shows that, although the time course for surviving visual acuity was markedly different by genotype, the time course for surviving visual field was not significantly different in the two groups of patients. Because our clinical impression has been that patients with X-linked retinitis pigmentosa are left with a small central island of vision at a younger age than patients with dominant retinitis pigmentosa, we repeated the visual field survival comparison after subtracting peripheral islands from field area and then censoring baseline field areas >4915 deg2, to exclude fields with large peripheral areas connected by a narrow bridge to the central field. We found a significant effect of genotype on the age distribution for retaining central field (P < 0.001, Fig. 2 ). The median age for central field area decreasing to 314 deg2 or less was 22 years younger in the RPGR patients (37 years) than in the RHO patients (59 years). 
Optical Coherence Tomography
Five of the 10 RHO patients with available OCTs had reduced visual acuity associated with macular cysts and were not considered further. Of the remaining patients with tomograms, the five with RHO mutations had a mean visual acuity of 20/22 and the five with RPGR mutations had a mean visual acuity of 20/53 (Table 4) . This difference was significant (P = 0.002). Their mean retinal thicknesses at the foveal center were 171 and 104 μm, respectively. The thickness in the RHO patients is similar to the normal mean thickness for our test system (167 μm), 11 and that in the RPGR patients is significantly smaller than that in the RHO patients (t-test for unequal variances, P = 0.03). Figure 3shows a tomogram from a 40-year-old RHO patient with a visual acuity of 20/25 and from a 38-year-old RPGR patient with a visual acuity of 20/100. The patient with the RHO mutation had a normal retinal thickness profile, whereas the patient with the RPGR mutation had a broad foveal depression with attenuation of the outer nuclear layer centrally, indicating loss of central foveal cones. 
Discussion
The present study, based on data from two large cohorts observed for an average of 8 and 9 years, shows that patients with retinitis pigmentosa due to RPGR mutations lost Snellen visual acuity at more than twice the mean rate of patients with retinitis pigmentosa due to RHO mutations. Our survival analyses over the long term showed that the median age of legal blindness was much younger age in patients with RPGR mutations than in patients with RHO mutations. Our data also showed that becoming legally blind was due primarily to loss of visual acuity in RPGR patients and to loss of visual field in RHO patients. 
OCT recordings revealed that the difference in mean visual acuity between these two groups may be attributable to photoreceptor loss. The tomograms of one RPGR patient showed a broad thinning of the fovea resembling that in the tomograms of patients with Stargardt’s disease 17 or occult macular dystrophy. 18 When visual acuity was reduced in patients with RHO mutations, it tended to be associated with macular cysts. Study of OCTs from additional RHO patients and RPGR patients who have reduced visual acuity will reveal whether these features are characteristic of these two groups. 
We also found that patients with RPGR mutations lost visual field area to the V4e stimulus at a mean rate that was approximately 50% faster than that in patients with RHO mutations and were left with a central island of vision ≤20° at a younger median age than the RHO patients. This result suggests that the faster loss of visual acuity by the RPGR patients may be a consequence of their faster loss of central field, consistent with a significant correlation between visual acuity and central visual field diameter in retinitis pigmentosa. 19 However, the two groups had similar age distributions for retaining 20° of total visual field and had nearly identical mean rates of progression of the full-field cone ERG, which derives mostly from the peripheral retina. 
In a previous study based on single visits with adjustment for differences in age, we reported that patients with RPGR mutations in exons 1 to 14 had a borderline smaller mean visual field area (P = 0.04) and mean cone ERG amplitude (P = 0.06) than did patients with RPGR mutations in ORF15, 5 suggesting that the former group had more severe disease at a given age than did the latter group. In the present study we evaluated whether mean rates of disease progression were different in these two groups. We found that patients with exon 1 to 14 mutations lost ERG amplitude 50% faster than did patients with ORF15 mutations, whereas visual acuity and visual field area declined comparably in the two groups. We, therefore, conclude that RPGR mutations in exons 1 to 14 tend to cause a more rapid loss of peripheral cone retinal function than do mutations in ORF15. 
 
Table 1.
 
Baseline Ocular Function of Patients with RPGR Mutations in Exons 1 to 14
Table 1.
 
Baseline Ocular Function of Patients with RPGR Mutations in Exons 1 to 14
ID Mutation* Protein Age (y) VA, † OD VA, † OS VF, ‡ OD VF, ‡ OS ERG, § OD ERG, § OS
5843 c.186G→A Gly43Arg 26 20/50 20/40 1967 2410 0.45 0.49
410 c.187G→A Gly43Glu 30 20/60 20/50 1473 405 NA NA
6813 c.238G→T Gly60Val 18 20/40 20/50 289 299 1.11 1.43
845 c.415delT Leu119;Ter@131 19 20/100 20/400 NA NA 2.7 2.7
6947 c.415delT Leu119;Ter@131 30 20/60 20/50 NA NA 0.11 0.11
3933 c.438A→G Arg127Gly 19 20/200 20/60 87 280 NA NA
7539 c.438A→G Arg127Gly 25 20/50 20/40 2355 2464 0.02 0.09
6208 c.544_545delTT Phe162;Ter@165 31 20/50 20/50 1120 2141 0.13 0.2
19673 c.664C→A Ser202Ter 8 20/50 20/50 13371 13941 NA 6.28
5571 c.664C→A Ser202Ter 27 20/50 20/60 3893 4079 NA NA
116 c.806delC Ala249;Ter@296 27 20/200 20/70 7625 9005 NA NA
6004 c.896delT Phe279;Ter@297 27 20/50 20/50 2626 3379 0.29 0.43
15587 c.897_901delCTTTT Leu280;Ter@280 34 20/30 20/40 3603 3330 0.85 1.04
1053 c.928delA Glu290;Ter@297 34 20/40 20/40 512 209 NA NA
5784 c.964G→A Cys302Tyr 33 20/70 20/80 3563 3622 0.58 0.56
19353 c.1039T→G Leu327Ter 8 20/70 20/80 9533 9931 2.45 3.65
19351 c.1039T→G Leu327Ter 9 20/50 20/40 11535 10512 3.3 2.6
6082 c.1151_1152insT Ala365;Ter@376 24 20/40 20/30 2313 2166 0.05 0.06
582 c.1159delC Pro367;Ter@380 46 20/60 20/100 308 245 0.27 0.14
3157 c.1366G→A Gly436Asp 5 20/30 20/30 9985 0 8 8
1779 c.1366G→A Gly436Asp 17 20/50 20/25 11527 9769 15 NA
1591 c.1366G→A Gly436Asp 19 20/30 20/25 11608 10917 NA NA
11730 c.1366G→A Gly436Asp 47 20/200 20/100 4017 4624 1.93 2.38
7056 c.1435_1436delTC Val459;Ter@461 27 20/30 20/40 2356 3220 0.6 0.8
2981 c.1435_1436delTC Val459;Ter@461 31 20/30 20/25 3135 2925 NA NA
5714 c.1641_1644delACAA Thr528;Ter@531 33 20/70 20/50 2163 2396 0.22 0.19
3288 c.1806G→T Glu583Ter 25 20/50 20/70 NA NA NA NA
5955 IVS1+1G→A Unknown 41 20/60 20/60 3408 6374 7.23 7.29
15433 IVS7-1G→A Unknown 22 20/50 20/60 6022 8437 0.82 0.77
3044 IVS13-1G→A Unknown 12 20/30 20/30 9966 8800 NA NA
15521 IVS13-1G→A Unknown 31 20/20 20/400 7228 6359 3.87 3.92
1560 IVS3-6T→A Unknown 25 20/25 20/25 1991 1793 1.83 1.83
6737 IVS4_1G→C Unknown 22 20/40 20/30 9435 9626 0.43 0.31
Mean 26 20/45 20/46 4967 4789 2.27 1.97
Table 2.
 
Baseline Ocular Function of Patients with RPGR Mutations in ORF15
Table 2.
 
Baseline Ocular Function of Patients with RPGR Mutations in ORF15
ID Mutation* Protein Age (y) VA, † OD VA, † OS VF, ‡ OD VF, ‡ OS ERG, § OD ERG, § OS
7273 g.ORF15+82_83insA ORF15Asn27;Ter@43 13 20/30 20/40 3734 4151 0.6 0.6
15396 g.ORF15+327A→T ORF15Lys109Ter 25 20/30 20/30 8440 8051 2.59 2.51
15370 g.ORF15+369G→T ORF15Glu123Ter 34 20/80 20/80 4536 3952 5.59 4.4
6045 g.ORF15+423G→T ORF15Glu141Ter 31 20/70 20/200 834 305 0.21 0.27
6820 g.ORF15+465G→T ORF15Glu155Ter 28 20/40 20/40 2094 3293 0.44 0.59
19848 g.ORF15+465G→T ORF15Glu155Ter 34 20/40 20/50 2686 3471 0.77 0.86
7730 g.ORF15+481_484delGAGA ORF15Arg160;Ter@229 16 20/40 20/40 10076 12254 0.24 0.22
7258 g.ORF15+481_484delGAGA ORF15Arg160;Ter@229 17 20/50 20/50 9710 9710 0.2 0.13
3554 g.ORF15+483_484delGA ORF15Glu161;Ter@183 18 20/40 20/40 NA NA NA NA
6977 g.ORF15+483_484delGA ORF15Glu161;Ter@183 24 20/30 20/25 3099 3440 3.91 3.28
6219 g.ORF15+483_484delGA ORF15Glu161;Ter@183 33 20/60 20/400 3882 3493 1.11 0.51
2482 g.ORF15+499_502delAGGA ORF15Lys166;Ter@229 22 20/30 20/40 8020 7086 NA NA
7344 g.ORF15+507G→T ORF15Glu169Ter 17 20/25 20/20 9978 8544 1.3 1.8
5667 g.ORF15+507G→T ORF15Glu169Ter 19 20/20 20/25 12961 11504 4.21 5.43
5654 g.ORF15+507G→T ORF15Glu169Ter 30 20/400 20/40 1198 1552 0.4 0.4
6197 g.ORF15+507G→T ORF15Glu169Ter 33 20/40 20/40 NA NA NA NA
7073 g.ORF15+517_518delAG ORF15Glu172;Ter@183 24 20/40 20/40 1655 2364 0.32 0.23
3389 g.ORF15+614_615delAA ORF15Lys201;Ter@248 14 20/70 20/60 9936 11556 NA NA
7402 g.ORF15+614_615delAA ORF15Lys201;Ter@248 24 20/40 20/200 2652 1939 0.24 0.28
5740 g.ORF15+614_615delAA ORF15Lys201;Ter@248 34 20/60 20/400 5322 3884 2.86 2.71
5849 g.ORF15+650_653delAGAG ORF15Thr216;Ter@229 26 20/100 20/70 4868 5128 0.24 0.18
3794 g.ORF15+652_653delAG ORF15Glu217;Ter@248 26 20/70 20/30 NA NA NA NA
3248 g.ORF15+652_653delAG ORF15Glu217;Ter@248 14 20/30 20/30 NA NA NA 24
5935 g.ORF15+652_653delAG ORF15Glu217;Ter@248 16 20/25 20/30 2883 2332 0.59 0.59
11496 g.ORF15+652_653delAG ORF15Glu217;Ter@248 19 20/40 20/30 11851 11460 3.5 3.64
6631 g.ORF15+652_653delAG ORF15Glu217;Ter@248 19 20/30 20/80 2341 2604 1.6 1.53
125 g.ORF15+652_653delAG ORF15Glu217;Ter@248 21 20/30 20/40 NA NA NA NA
15290 g.ORF15+652_653delAG ORF15Glu217;Ter@248 26 20/100 20/80 4899 6706 2.36 3.9
5757 g.ORF15+652_653delAG ORF15Glu217;Ter@248 31 20/70 20/80 3328 4165 2.4 1.25
6857 g.ORF15+659_660delAG ORF15Arg219;Ter@248 15 20/30 20/30 12003 12491 1.2 2
6772 g.ORF15+659_660delAG ORF15Arg219;Ter@248 34 20/70 20/60 2717 2591 0.72 0.54
14309 g.ORF15+670_671delAA ORF15Lys223;Ter@248 8 20/30 20/30 8874 8360 6.09 6.16
1924 g.ORF15+670_671delAA ORF15Lys223;Ter@248 21 20/30 20/40 6800 6024 17 17
14066 g.ORF15+673_674delAG ORF15Glu224;Ter@248 16 20/30 20/20 6936 10409 13 13
7364 g.ORF15+673_674delAG ORF15Glu224;Ter@248 29 20/50 20/40 616 1139 0.08 0.16
1886 g.ORF15+673_674delAG ORF15Glu224;Ter@248 31 20/100 20/200 NA NA NA NA
156 g.ORF15+673_674delAG ORF15Glu224;Ter@248 33 20/400 20/400 NA NA NA NA
13290 g.ORF15+684G→T ORF15Glu228Ter 8 20/70 20/70 8460 11008 1.47 1.05
5656 g.ORF15+689_692delAGAG ORF15Val229;Ter@234 21 20/400 20/400 5338 5443 NA NA
7038 g.ORF15+689_692delAGAG ORF15Val229;Ter@234 30 20/70 20/70 3997 3912 1.75 1.37
14362 g.ORF15+738G→T ORF15Glu246Ter 22 20/70 20/80 692 741 0.09 0.09
15438 g.ORF15+740_741delGG ORF15Glu246;Ter@248 7 20/50 20/50 NA NA 4.41 3.5
2554 g.ORF15+746delT ORF15Gly248;Ter@503 31 20/60 20/50 6787 7166 NA NA
1175 g.ORF15+752_753delGG ORF15Gly250;Ter@492 19 20/30 20/50 6015 6485 NA NA
6154 g.ORF15+763_767delAAGGG ORF15Glu254;Ter492 20 20/40 20/40 7363 5978 2.13 2.37
1887 g.ORF15+818_819delAG ORF15Lys272;Ter@492 17 20/40 20/30 NA NA 0.3 0.3
4025 g.ORF15+818_819delAG ORF15Lys272;Ter@492 22 20/50 20/50 1785 739 NA NA
1888 g.ORF15+818_819delAG ORF15Lys272;Ter@492 29 20/40 20/40 NA NA NA 1.3
2964 g.ORF15+818_819delAG ORF15Lys272;Ter@492 54 HM 20/200 NA NA NA NA
5987 g.ORF15+872_873insA ORF15Gly291;Ter@492 27 20/70 20/200 4370 4848 NA NA
5927 g.ORF15+897G→T ORF15Glu299Ter 21 20/30 20/30 3202 3893 5.99 6.07
7983 g.ORF15+902_903delGG ORF15Gly300;Ter@492 8 20/25 20/25 12014 9532 2.17 2.3
6471 g.ORF15+902_903delGG ORF15Gly300;Ter@492 31 20/50 20/100 6014 5042 2.01 2.22
15596 g.ORF15+872_873insA ORF15Gly291;Ter@492 27 20/50 20/40 NA NA 2.24 2.7
43 g.ORF15+906_909delGGAG ORF15Gly302;Ter@503 12 20/40 20/200 NA NA NA NA
15133 g.ORF15+926_927delGG ORF15Gly308;Ter@492 32 20/50 20/60 NA NA NA NA
1781 g.ORF15+954G→T ORF15Glu318Ter 40 CF@10ft CF@5ft NA NA NA NA
14443 g.ORF15+954G→T ORF15Glu318Ter 61 CF@10ft CF@5ft 1986 1444 NA NA
5996 g.ORF15+961_962delAA ORF15Glu320;Ter492 29 20/60 20/40 4290 4727 2.63 2.02
11425 g.ORF15+962-963insCCTC ORF15Glu321;Ter@492 40 20/60 20/100 361 363 0.49 0.28
1158 g.ORF15+963G→T ORF15Glu321Ter 30 20/60 20/60 1390 1665 NA NA
15908 g.ORF15+977_978delGG ORF15Gly325;Ter@492 42 20/200 20/100 NA NA 2.55 2.66
5923 g.ORF15+1010_1011delGG ORF15Gly336;Ter@492 31 20/50 20/50 671 566 0.25 0.17
6480 g.ORF15+1047G→T ORF15Glu349Ter 21 20/40 20/60 3560 3593 1.76 1.08
6184 g.ORF15+1113delG ORF15Glu371;Ter@503 18 20/40 20/50 5774 6889 0.08 0.13
6719 g.ORF15+1146delG ORF15Glu382;Ter@503 18 20/50 20/40 5514 9059 0.78 0.49
6079 g.ORF15+1146delG ORF15Glu382;Ter@503 37 20/50 20/70 6783 5170 3.14 2.68
15805 g.ORF15+1184_1185delGG ORF15Gly394;Ter@492 15 20/80 20/60 7622 8933 7.2 7.3
5852 g.ORF15+1184_1185delGG ORF15Gly394;Ter@492 18 20/50 20/60 4704 9035 1.5 1.4
5741 g.ORF15+1191delG ORF15Glu397;Ter@503 41 20/40 20/40 4864 4832 4.38 3.02
3892 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 26 CF@10ft 20/80 9681 9090 NA NA
7748 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 26 20/70 20/80 9936 9355 0.7 1.4
3894 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 28 20/50 20/60 9391 9138 NA NA
7843 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 35 20/200 20/400 7347 8452 1.62 2.16
15151 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 40 20/400 20/400 NA NA 4.2 5.6
5754 g.ORF15+1258_1259delAG ORF15Glu419;Ter@492 25 20/200 20/50 609 930 0.06 0.12
7555 g.ORF15+1339_1340delAG ORF15Glu446;Ter@493 45 20/80 20/30 7288 6602 13 13
6889 g.ORF15+1339delA ORF15Glu446;Ter@503 20 20/30 20/25 15537 13333 6.9 7.38
6635 g.ORF15+1339delA ORF15Glu446;Ter@503 25 20/40 20/50 619 1065 0.14 0.12
14072 g.ORF15+1343_1344delGG ORF15Gly447;Ter@493 47 20/200 20/200 12026 12153 3.92 4.2
Mean 26 20/49 20/51 5634 5796 2.66 2.99
Table 3.
 
Annual Rates of Change in Patients with RPGR Mutations
Table 3.
 
Annual Rates of Change in Patients with RPGR Mutations
Ocular Function n * Mean ± SEM, † P , †
Loge visual acuity 93 −0.041 ± 0.003 <0.001
Loge visual field area 102 −0.048 ± 0.004 <0.001
Loge ERG amplitude 60 −0.074 ± 0.006 <0.001
Figure 1.
 
Weibull plot survival analysis for legal blindness (i.e., loss of acuity and/or field) by genotype. The effect of genotype was significant (Wald χ2 test, P < 0.001). Vertical lines: median age of legal blindness in patients with RPGR mutations (left) and in patients with RHO mutations (right).
Figure 1.
 
Weibull plot survival analysis for legal blindness (i.e., loss of acuity and/or field) by genotype. The effect of genotype was significant (Wald χ2 test, P < 0.001). Vertical lines: median age of legal blindness in patients with RPGR mutations (left) and in patients with RHO mutations (right).
Figure 2.
 
Weibull plot survival analysis for a visual acuity >20/200 (blue curves) or a visual field area >314 deg2 (i.e., an equivalent diameter of 20°, green curves) by genotype. Visual field survival is also shown for the central field, excluding peripheral islands (red curves). The effect of genotype was significant for visual acuity (P < 0.001) and for central field (P < 0.001), but not for total field (P = 0.29).
Figure 2.
 
Weibull plot survival analysis for a visual acuity >20/200 (blue curves) or a visual field area >314 deg2 (i.e., an equivalent diameter of 20°, green curves) by genotype. Visual field survival is also shown for the central field, excluding peripheral islands (red curves). The effect of genotype was significant for visual acuity (P < 0.001) and for central field (P < 0.001), but not for total field (P = 0.29).
Table 4.
 
Visual Acuity and Central Foveal Thickness by Genotype in Retinitis Pigmentosa
Table 4.
 
Visual Acuity and Central Foveal Thickness by Genotype in Retinitis Pigmentosa
Genotype ID Age (y) Visual Acuity* Central Foveal Thickness (μm)*
RHO 19400 26 20/20 156
15594 39 20/20 187
19785 40 20/25 172
19173 41 20/30 165
19582 43 20/20 173
RPGR 14309 19 20/30 134
15396 32 20/44 147.5
11496 33 20/114 37
15133 38 20/89 83.5
1888 47 20/55 117
Figure 3.
 
Tomograms subtending 20° (Stratus High-resolution Optical Coherence Tomographer [OCT3], Carl Zeiss Meditec, Inc., Dublin, CA) from the right eye of a 40-year-old woman with dominant retinitis pigmentosa due to an RHO mutation (Pro23His) and visual acuity of 20/25 (left) and from the right eye of a 38-year-old man with X-linked retinitis pigmentosa due to an RPGR mutation (ORF15Gly308;Ter@492) and visual acuity of 20/100 (right). ONL, outer nuclear layer.
Figure 3.
 
Tomograms subtending 20° (Stratus High-resolution Optical Coherence Tomographer [OCT3], Carl Zeiss Meditec, Inc., Dublin, CA) from the right eye of a 40-year-old woman with dominant retinitis pigmentosa due to an RHO mutation (Pro23His) and visual acuity of 20/25 (left) and from the right eye of a 38-year-old man with X-linked retinitis pigmentosa due to an RPGR mutation (ORF15Gly308;Ter@492) and visual acuity of 20/100 (right). ONL, outer nuclear layer.
The authors thank Terri L. McGee for help in compiling the list of RPGR mutations. 
BersonEL, SandbergMA, RosnerB, et al. Natural course of retinitis pigmentosa over a three-year interval. Am J Ophthalmol. 1985;99:240–251. [CrossRef] [PubMed]
BersonEL, RosnerB, Weigel-DiFrancoC, DryjaTP, SandbergMA. Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations. Invest Ophthalmol Vis Sci. 2002;43:3027–3036. [PubMed]
HongD, PawlykBS, ShangJ, et al. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model of X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci USA. 2000;97:3649–3654. [CrossRef] [PubMed]
SharonD, BrunsGAP, McGeeTL, SandbergMA, BersonEL, DryjaT. X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function. Invest Ophthalmol Vis Sci. 2000;41:2712–2721. [PubMed]
SharonD, SandbergMA, RabeVW, StillbergerM, DryjaTP, BersonEL. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet. 2003;73:1131–1146. [CrossRef] [PubMed]
KirkhamTH, MeyerE. Visual field area on the Goldmann hemispheric perimeter surface: correction of cartographic errors inherent in perimetry. Curr Eye Res. 1981;1:93–99. [CrossRef] [PubMed]
DrasdoN, FowlerCW. Non-linear projection of the retinal image in a wide-angle schematic eye. Br J Ophthalmol. 1974;58:709–714. [CrossRef] [PubMed]
HolopigianK, GreensteinV, SeipleW, CarrRE. Rates of change differ among measures of visual function in patients with retinitis pigmentosa. Ophthalmology. 1996;103:398–405. [CrossRef] [PubMed]
GroverS, FishmanGA, AndersonRJ, AlexanderKR, DerlackiDJ. Rate of visual field loss in retinitis pigmentosa. Ophthalmology. 1997;104:460–465. [CrossRef] [PubMed]
IannacconeA, KritchevskySB, CiccarelliML, et al. Kinetics of visual field loss in Usher Syndrome type II. Invest Ophthalmol Vis Sci. 2004;45:784–792. [CrossRef] [PubMed]
SandbergMA, BrockhurstRJ, GaudioAR, BersonEL. The association between visual acuity and central retinal thickness in retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2005;46:3349–3354. [CrossRef] [PubMed]
ClarkeG, CollinsRA, LeavittBR, et al. A one-hit model of cell death in inherited neuronal degenerations. Nature. 2000;406:195–199. [CrossRef] [PubMed]
MassofRW, DagnelieG, BenzschawelT, PalmerRW, FinkelsteinD. First order dynamics of visual field loss in retinitis pigmentosa. Clin Vis Sci. 1990;5:1–26.
BirchDG, AndersonJL, FishGE. Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy. Ophthalmology. 1999;106:258–268. [CrossRef] [PubMed]
MeindlA, DryK, HerrmannK, et al. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat Genet. 1996;13:35–42. [CrossRef] [PubMed]
VervoortT, LennonA, BirdAC, et al. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nat Genet. 2000;25:462–466. [CrossRef] [PubMed]
ErgunE, HermannB, WirtitschM, et al. Assessment of central visual function in Stargardt’s disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2005;46:310–316. [CrossRef] [PubMed]
BrockhurstRJ, SandbergMA. Optical coherence findings in occult macular dystrophy. Am J Ophthalmol. 2007;143:516–518. [CrossRef] [PubMed]
MadreperlaSA, PalmerRW, MassofRW, FinkelsteinD. Visual acuity loss in retinitis pigmentosa: relationship to visual field loss. Arch Ophthalmol. 1990;108:358–361. [CrossRef] [PubMed]
Figure 1.
 
Weibull plot survival analysis for legal blindness (i.e., loss of acuity and/or field) by genotype. The effect of genotype was significant (Wald χ2 test, P < 0.001). Vertical lines: median age of legal blindness in patients with RPGR mutations (left) and in patients with RHO mutations (right).
Figure 1.
 
Weibull plot survival analysis for legal blindness (i.e., loss of acuity and/or field) by genotype. The effect of genotype was significant (Wald χ2 test, P < 0.001). Vertical lines: median age of legal blindness in patients with RPGR mutations (left) and in patients with RHO mutations (right).
Figure 2.
 
Weibull plot survival analysis for a visual acuity >20/200 (blue curves) or a visual field area >314 deg2 (i.e., an equivalent diameter of 20°, green curves) by genotype. Visual field survival is also shown for the central field, excluding peripheral islands (red curves). The effect of genotype was significant for visual acuity (P < 0.001) and for central field (P < 0.001), but not for total field (P = 0.29).
Figure 2.
 
Weibull plot survival analysis for a visual acuity >20/200 (blue curves) or a visual field area >314 deg2 (i.e., an equivalent diameter of 20°, green curves) by genotype. Visual field survival is also shown for the central field, excluding peripheral islands (red curves). The effect of genotype was significant for visual acuity (P < 0.001) and for central field (P < 0.001), but not for total field (P = 0.29).
Figure 3.
 
Tomograms subtending 20° (Stratus High-resolution Optical Coherence Tomographer [OCT3], Carl Zeiss Meditec, Inc., Dublin, CA) from the right eye of a 40-year-old woman with dominant retinitis pigmentosa due to an RHO mutation (Pro23His) and visual acuity of 20/25 (left) and from the right eye of a 38-year-old man with X-linked retinitis pigmentosa due to an RPGR mutation (ORF15Gly308;Ter@492) and visual acuity of 20/100 (right). ONL, outer nuclear layer.
Figure 3.
 
Tomograms subtending 20° (Stratus High-resolution Optical Coherence Tomographer [OCT3], Carl Zeiss Meditec, Inc., Dublin, CA) from the right eye of a 40-year-old woman with dominant retinitis pigmentosa due to an RHO mutation (Pro23His) and visual acuity of 20/25 (left) and from the right eye of a 38-year-old man with X-linked retinitis pigmentosa due to an RPGR mutation (ORF15Gly308;Ter@492) and visual acuity of 20/100 (right). ONL, outer nuclear layer.
Table 1.
 
Baseline Ocular Function of Patients with RPGR Mutations in Exons 1 to 14
Table 1.
 
Baseline Ocular Function of Patients with RPGR Mutations in Exons 1 to 14
ID Mutation* Protein Age (y) VA, † OD VA, † OS VF, ‡ OD VF, ‡ OS ERG, § OD ERG, § OS
5843 c.186G→A Gly43Arg 26 20/50 20/40 1967 2410 0.45 0.49
410 c.187G→A Gly43Glu 30 20/60 20/50 1473 405 NA NA
6813 c.238G→T Gly60Val 18 20/40 20/50 289 299 1.11 1.43
845 c.415delT Leu119;Ter@131 19 20/100 20/400 NA NA 2.7 2.7
6947 c.415delT Leu119;Ter@131 30 20/60 20/50 NA NA 0.11 0.11
3933 c.438A→G Arg127Gly 19 20/200 20/60 87 280 NA NA
7539 c.438A→G Arg127Gly 25 20/50 20/40 2355 2464 0.02 0.09
6208 c.544_545delTT Phe162;Ter@165 31 20/50 20/50 1120 2141 0.13 0.2
19673 c.664C→A Ser202Ter 8 20/50 20/50 13371 13941 NA 6.28
5571 c.664C→A Ser202Ter 27 20/50 20/60 3893 4079 NA NA
116 c.806delC Ala249;Ter@296 27 20/200 20/70 7625 9005 NA NA
6004 c.896delT Phe279;Ter@297 27 20/50 20/50 2626 3379 0.29 0.43
15587 c.897_901delCTTTT Leu280;Ter@280 34 20/30 20/40 3603 3330 0.85 1.04
1053 c.928delA Glu290;Ter@297 34 20/40 20/40 512 209 NA NA
5784 c.964G→A Cys302Tyr 33 20/70 20/80 3563 3622 0.58 0.56
19353 c.1039T→G Leu327Ter 8 20/70 20/80 9533 9931 2.45 3.65
19351 c.1039T→G Leu327Ter 9 20/50 20/40 11535 10512 3.3 2.6
6082 c.1151_1152insT Ala365;Ter@376 24 20/40 20/30 2313 2166 0.05 0.06
582 c.1159delC Pro367;Ter@380 46 20/60 20/100 308 245 0.27 0.14
3157 c.1366G→A Gly436Asp 5 20/30 20/30 9985 0 8 8
1779 c.1366G→A Gly436Asp 17 20/50 20/25 11527 9769 15 NA
1591 c.1366G→A Gly436Asp 19 20/30 20/25 11608 10917 NA NA
11730 c.1366G→A Gly436Asp 47 20/200 20/100 4017 4624 1.93 2.38
7056 c.1435_1436delTC Val459;Ter@461 27 20/30 20/40 2356 3220 0.6 0.8
2981 c.1435_1436delTC Val459;Ter@461 31 20/30 20/25 3135 2925 NA NA
5714 c.1641_1644delACAA Thr528;Ter@531 33 20/70 20/50 2163 2396 0.22 0.19
3288 c.1806G→T Glu583Ter 25 20/50 20/70 NA NA NA NA
5955 IVS1+1G→A Unknown 41 20/60 20/60 3408 6374 7.23 7.29
15433 IVS7-1G→A Unknown 22 20/50 20/60 6022 8437 0.82 0.77
3044 IVS13-1G→A Unknown 12 20/30 20/30 9966 8800 NA NA
15521 IVS13-1G→A Unknown 31 20/20 20/400 7228 6359 3.87 3.92
1560 IVS3-6T→A Unknown 25 20/25 20/25 1991 1793 1.83 1.83
6737 IVS4_1G→C Unknown 22 20/40 20/30 9435 9626 0.43 0.31
Mean 26 20/45 20/46 4967 4789 2.27 1.97
Table 2.
 
Baseline Ocular Function of Patients with RPGR Mutations in ORF15
Table 2.
 
Baseline Ocular Function of Patients with RPGR Mutations in ORF15
ID Mutation* Protein Age (y) VA, † OD VA, † OS VF, ‡ OD VF, ‡ OS ERG, § OD ERG, § OS
7273 g.ORF15+82_83insA ORF15Asn27;Ter@43 13 20/30 20/40 3734 4151 0.6 0.6
15396 g.ORF15+327A→T ORF15Lys109Ter 25 20/30 20/30 8440 8051 2.59 2.51
15370 g.ORF15+369G→T ORF15Glu123Ter 34 20/80 20/80 4536 3952 5.59 4.4
6045 g.ORF15+423G→T ORF15Glu141Ter 31 20/70 20/200 834 305 0.21 0.27
6820 g.ORF15+465G→T ORF15Glu155Ter 28 20/40 20/40 2094 3293 0.44 0.59
19848 g.ORF15+465G→T ORF15Glu155Ter 34 20/40 20/50 2686 3471 0.77 0.86
7730 g.ORF15+481_484delGAGA ORF15Arg160;Ter@229 16 20/40 20/40 10076 12254 0.24 0.22
7258 g.ORF15+481_484delGAGA ORF15Arg160;Ter@229 17 20/50 20/50 9710 9710 0.2 0.13
3554 g.ORF15+483_484delGA ORF15Glu161;Ter@183 18 20/40 20/40 NA NA NA NA
6977 g.ORF15+483_484delGA ORF15Glu161;Ter@183 24 20/30 20/25 3099 3440 3.91 3.28
6219 g.ORF15+483_484delGA ORF15Glu161;Ter@183 33 20/60 20/400 3882 3493 1.11 0.51
2482 g.ORF15+499_502delAGGA ORF15Lys166;Ter@229 22 20/30 20/40 8020 7086 NA NA
7344 g.ORF15+507G→T ORF15Glu169Ter 17 20/25 20/20 9978 8544 1.3 1.8
5667 g.ORF15+507G→T ORF15Glu169Ter 19 20/20 20/25 12961 11504 4.21 5.43
5654 g.ORF15+507G→T ORF15Glu169Ter 30 20/400 20/40 1198 1552 0.4 0.4
6197 g.ORF15+507G→T ORF15Glu169Ter 33 20/40 20/40 NA NA NA NA
7073 g.ORF15+517_518delAG ORF15Glu172;Ter@183 24 20/40 20/40 1655 2364 0.32 0.23
3389 g.ORF15+614_615delAA ORF15Lys201;Ter@248 14 20/70 20/60 9936 11556 NA NA
7402 g.ORF15+614_615delAA ORF15Lys201;Ter@248 24 20/40 20/200 2652 1939 0.24 0.28
5740 g.ORF15+614_615delAA ORF15Lys201;Ter@248 34 20/60 20/400 5322 3884 2.86 2.71
5849 g.ORF15+650_653delAGAG ORF15Thr216;Ter@229 26 20/100 20/70 4868 5128 0.24 0.18
3794 g.ORF15+652_653delAG ORF15Glu217;Ter@248 26 20/70 20/30 NA NA NA NA
3248 g.ORF15+652_653delAG ORF15Glu217;Ter@248 14 20/30 20/30 NA NA NA 24
5935 g.ORF15+652_653delAG ORF15Glu217;Ter@248 16 20/25 20/30 2883 2332 0.59 0.59
11496 g.ORF15+652_653delAG ORF15Glu217;Ter@248 19 20/40 20/30 11851 11460 3.5 3.64
6631 g.ORF15+652_653delAG ORF15Glu217;Ter@248 19 20/30 20/80 2341 2604 1.6 1.53
125 g.ORF15+652_653delAG ORF15Glu217;Ter@248 21 20/30 20/40 NA NA NA NA
15290 g.ORF15+652_653delAG ORF15Glu217;Ter@248 26 20/100 20/80 4899 6706 2.36 3.9
5757 g.ORF15+652_653delAG ORF15Glu217;Ter@248 31 20/70 20/80 3328 4165 2.4 1.25
6857 g.ORF15+659_660delAG ORF15Arg219;Ter@248 15 20/30 20/30 12003 12491 1.2 2
6772 g.ORF15+659_660delAG ORF15Arg219;Ter@248 34 20/70 20/60 2717 2591 0.72 0.54
14309 g.ORF15+670_671delAA ORF15Lys223;Ter@248 8 20/30 20/30 8874 8360 6.09 6.16
1924 g.ORF15+670_671delAA ORF15Lys223;Ter@248 21 20/30 20/40 6800 6024 17 17
14066 g.ORF15+673_674delAG ORF15Glu224;Ter@248 16 20/30 20/20 6936 10409 13 13
7364 g.ORF15+673_674delAG ORF15Glu224;Ter@248 29 20/50 20/40 616 1139 0.08 0.16
1886 g.ORF15+673_674delAG ORF15Glu224;Ter@248 31 20/100 20/200 NA NA NA NA
156 g.ORF15+673_674delAG ORF15Glu224;Ter@248 33 20/400 20/400 NA NA NA NA
13290 g.ORF15+684G→T ORF15Glu228Ter 8 20/70 20/70 8460 11008 1.47 1.05
5656 g.ORF15+689_692delAGAG ORF15Val229;Ter@234 21 20/400 20/400 5338 5443 NA NA
7038 g.ORF15+689_692delAGAG ORF15Val229;Ter@234 30 20/70 20/70 3997 3912 1.75 1.37
14362 g.ORF15+738G→T ORF15Glu246Ter 22 20/70 20/80 692 741 0.09 0.09
15438 g.ORF15+740_741delGG ORF15Glu246;Ter@248 7 20/50 20/50 NA NA 4.41 3.5
2554 g.ORF15+746delT ORF15Gly248;Ter@503 31 20/60 20/50 6787 7166 NA NA
1175 g.ORF15+752_753delGG ORF15Gly250;Ter@492 19 20/30 20/50 6015 6485 NA NA
6154 g.ORF15+763_767delAAGGG ORF15Glu254;Ter492 20 20/40 20/40 7363 5978 2.13 2.37
1887 g.ORF15+818_819delAG ORF15Lys272;Ter@492 17 20/40 20/30 NA NA 0.3 0.3
4025 g.ORF15+818_819delAG ORF15Lys272;Ter@492 22 20/50 20/50 1785 739 NA NA
1888 g.ORF15+818_819delAG ORF15Lys272;Ter@492 29 20/40 20/40 NA NA NA 1.3
2964 g.ORF15+818_819delAG ORF15Lys272;Ter@492 54 HM 20/200 NA NA NA NA
5987 g.ORF15+872_873insA ORF15Gly291;Ter@492 27 20/70 20/200 4370 4848 NA NA
5927 g.ORF15+897G→T ORF15Glu299Ter 21 20/30 20/30 3202 3893 5.99 6.07
7983 g.ORF15+902_903delGG ORF15Gly300;Ter@492 8 20/25 20/25 12014 9532 2.17 2.3
6471 g.ORF15+902_903delGG ORF15Gly300;Ter@492 31 20/50 20/100 6014 5042 2.01 2.22
15596 g.ORF15+872_873insA ORF15Gly291;Ter@492 27 20/50 20/40 NA NA 2.24 2.7
43 g.ORF15+906_909delGGAG ORF15Gly302;Ter@503 12 20/40 20/200 NA NA NA NA
15133 g.ORF15+926_927delGG ORF15Gly308;Ter@492 32 20/50 20/60 NA NA NA NA
1781 g.ORF15+954G→T ORF15Glu318Ter 40 CF@10ft CF@5ft NA NA NA NA
14443 g.ORF15+954G→T ORF15Glu318Ter 61 CF@10ft CF@5ft 1986 1444 NA NA
5996 g.ORF15+961_962delAA ORF15Glu320;Ter492 29 20/60 20/40 4290 4727 2.63 2.02
11425 g.ORF15+962-963insCCTC ORF15Glu321;Ter@492 40 20/60 20/100 361 363 0.49 0.28
1158 g.ORF15+963G→T ORF15Glu321Ter 30 20/60 20/60 1390 1665 NA NA
15908 g.ORF15+977_978delGG ORF15Gly325;Ter@492 42 20/200 20/100 NA NA 2.55 2.66
5923 g.ORF15+1010_1011delGG ORF15Gly336;Ter@492 31 20/50 20/50 671 566 0.25 0.17
6480 g.ORF15+1047G→T ORF15Glu349Ter 21 20/40 20/60 3560 3593 1.76 1.08
6184 g.ORF15+1113delG ORF15Glu371;Ter@503 18 20/40 20/50 5774 6889 0.08 0.13
6719 g.ORF15+1146delG ORF15Glu382;Ter@503 18 20/50 20/40 5514 9059 0.78 0.49
6079 g.ORF15+1146delG ORF15Glu382;Ter@503 37 20/50 20/70 6783 5170 3.14 2.68
15805 g.ORF15+1184_1185delGG ORF15Gly394;Ter@492 15 20/80 20/60 7622 8933 7.2 7.3
5852 g.ORF15+1184_1185delGG ORF15Gly394;Ter@492 18 20/50 20/60 4704 9035 1.5 1.4
5741 g.ORF15+1191delG ORF15Glu397;Ter@503 41 20/40 20/40 4864 4832 4.38 3.02
3892 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 26 CF@10ft 20/80 9681 9090 NA NA
7748 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 26 20/70 20/80 9936 9355 0.7 1.4
3894 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 28 20/50 20/60 9391 9138 NA NA
7843 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 35 20/200 20/400 7347 8452 1.62 2.16
15151 g.ORF15+1254_1257delGGAG ORF15Gly418;Ter@503 40 20/400 20/400 NA NA 4.2 5.6
5754 g.ORF15+1258_1259delAG ORF15Glu419;Ter@492 25 20/200 20/50 609 930 0.06 0.12
7555 g.ORF15+1339_1340delAG ORF15Glu446;Ter@493 45 20/80 20/30 7288 6602 13 13
6889 g.ORF15+1339delA ORF15Glu446;Ter@503 20 20/30 20/25 15537 13333 6.9 7.38
6635 g.ORF15+1339delA ORF15Glu446;Ter@503 25 20/40 20/50 619 1065 0.14 0.12
14072 g.ORF15+1343_1344delGG ORF15Gly447;Ter@493 47 20/200 20/200 12026 12153 3.92 4.2
Mean 26 20/49 20/51 5634 5796 2.66 2.99
Table 3.
 
Annual Rates of Change in Patients with RPGR Mutations
Table 3.
 
Annual Rates of Change in Patients with RPGR Mutations
Ocular Function n * Mean ± SEM, † P , †
Loge visual acuity 93 −0.041 ± 0.003 <0.001
Loge visual field area 102 −0.048 ± 0.004 <0.001
Loge ERG amplitude 60 −0.074 ± 0.006 <0.001
Table 4.
 
Visual Acuity and Central Foveal Thickness by Genotype in Retinitis Pigmentosa
Table 4.
 
Visual Acuity and Central Foveal Thickness by Genotype in Retinitis Pigmentosa
Genotype ID Age (y) Visual Acuity* Central Foveal Thickness (μm)*
RHO 19400 26 20/20 156
15594 39 20/20 187
19785 40 20/25 172
19173 41 20/30 165
19582 43 20/20 173
RPGR 14309 19 20/30 134
15396 32 20/44 147.5
11496 33 20/114 37
15133 38 20/89 83.5
1888 47 20/55 117
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