Gene augmentation for X-linked retinitis pigmentosa caused by mutations in RPGR

Cold Spring Harbor Perspectives in Medicine

Volumn 5, Issue 2, 2015, Pages

  Beltran, William A ^a   Cideciyan, Artur V ^b   Lewin, Alfred S ^c   Hauswirth, William W ^d   Jacobson, Samuel G ^b   Aguirre, Gustavo D ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

^d UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

VIRUS VECTOR; CARRIER PROTEIN; EYE PROTEIN; RPGR PROTEIN, HUMAN; RPGR PROTEIN, MOUSE;

ARTICLE; CANINE MODEL; EXPERIMENTAL DOG; GENE; GENE MUTATION; GENE THERAPY; GENE TRANSFER; HUMAN; MURINE MODEL; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; PHENOTYPE; PHOTORECEPTOR; PHOTORECEPTOR CONNECTING CILIUM; PROMOTER REGION; RETINA DEGENERATION; RETINITIS PIGMENTOSA; RPGR GENE; TREATMENT FAILURE; X CHROMOSOME LINKED DISORDER; X LINKED RETINITIS PIGMENTOSA; ANIMAL; DISEASE MODEL; DOG; FEMALE; GENETIC DISEASES, X-LINKED; GENETIC LINKAGE; GENETICS; MALE; MOUSE; MUTATION; TREATMENT OUTCOME;

ANIMALS; CARRIER PROTEINS; DISEASE MODELS, ANIMAL; DOGS; EYE PROTEINS; FEMALE; GENETIC DISEASES, X-LINKED; GENETIC LINKAGE; GENETIC THERAPY; HUMANS; MALE; MICE; MUTATION; PHENOTYPE; RETINITIS PIGMENTOSA; TREATMENT OUTCOME;

EID: 84923804350     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a017392     Document Type: Article

References (93)

1. Adamian M, Pawlyk BS, Hong DH, Berson EL. 2006. Rod and cone opsin mislocalization in an autopsy eye from a carrier of X-linked retinitis pigmentosa with a Gly436Asp mutation in the RPGR gene. Am J Ophthalmol 142: 515– 518.
2. Aguirre GD, Yashar BM, John SK, Smith JE, Breuer DK, Hiriyanna S, Swaroop A, Milam AH. 2002. Retinal histo pathology of an XLRP carrier with a mutation in the RPGR exon ORF15. Exp Eye Res 75: 431–443
3. al-Ubaidi MR, Font RL, Quiambao AB, Keener MJ, Liou GI, Overbeek PA, Baehr W. 1992. Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. J Cell Biol 119: 1681–1687.
4. Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Roman AJ, Windsor EA, Steinberg JD, Branham K, Othman M, Swaroop A, et al. 2007. Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations. Invest Ophthalmol Vis Sci 48: 4759–4765.
5. Andreasson S, Ponjavic V, Abrahamson M, Ehinger B, Wu W, Fujita R, Buraczynska M, Swaroop A. 1997. Phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. Am J Ophthalmol 124: 95–102.
6. Ayyagari R, Demirci FY, Liu J, Bingham EL, Stringham H, Kakuk LE, Boehnke M, Gorin MB, Richards JE, Sieving PA. 2002. X-linked recessive atrophic macular degeneration from RPGR mutation. Genomics 80: 166–171.
7. Bader I, Brandau O, Achatz H, Apfelstedt-Sylla E, Hergersberg M, Lorenz B, Wissinger B, Wittwer B, Rudolph G, Meindl A, et al. 2003. X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15. Invest Ophthalmol Vis Sci 44: 1458–1463.
8. Bauer S, Fujita R, Buraczynska M, Abrahamson M, Ehinger B, Wu W, Falls TJ, Andreasson S, Swaroop A. 1998. Phenotype of an X-linked retinitis pigmentosa family with a novel splice defect in the RPGR gene. Invest Ophthalmol Vis Sci 39: 2470–2474.
9. Beltran WA. 2009. The use of canine models of inherited retinal degeneration to test novel therapeutic approaches. Vet Ophthalmol 12: 192–204.
10. Beltran WA, Hammond P, Acland GM, Aguirre GD. 2006. A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 47: 1669–1681.
11. Beltran WA, Wen R, Acland GM, Aguirre GD. 2007. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina. Exp Eye Res 84: 753–771.
12. Beltran WA, Acland GM, Aguirre GD. 2009. Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGRexon ORF15 mutations. Invest Ophthalmol Vis Sci 50: 3985–3995.
13. Beltran WA, Boye SL, Boye SE, Chiodo VA, Lewin AS, Hauswirth WW, Aguirre GD. 2010. rAAV2/5 gene-targeting to rods:dose-dependent efficiency and complications associated with different promoters. Gene Ther 17: 1162– 1174.
14. Beltran WA, Iwabe S, Fajardo D, Boye SE, Teng W-T, Hauswirth WW, Lewin AS, Aguirre GD. 2011. rAAV-mediated gene delivery of truncated canine RPGR causes photoreceptor dysplasia in dogs with RPGR-ORF15 stop mutation. Association for Research in Vision and Ophthalmology, 1–5 May, E-abstract 1418, Fort Lauderdale, FL.
15. Beltran WA, Cideciyan AV, Lewin AS, Iwabe S, Khanna H, Sumaroka A, Chiodo V, Fajardo DS, Roman AJ, Deng WT, et al. 2012. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci 109: 2132–2137.
16. Beltran WA, Cideciyan AV, Lewin AS, Iwabe S, Boye S, Hauswirth WW, Jacobson SG, Aguirre GD. 2013. Corrective gene therapy for RPGR-XLRP rescues a canine model at mid-stage disease. Association for Research in Vision & Ophthalmology, 5–9 May, E-abstract 2707, Seattle, WA.
17. Beltran WA, Cideciyan AV, Guziewicz KE, Iwabe S, Swider M, Scott EM, Savina SV, Ruthel G, Stefano F, Zhang L, et al. 2014a. Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations. PLoS ONE 9: e90390. doi:10.1371/journal.pone/0090390.
18. Beltran WA, Cideciyan AV, Lewin AS, Iwabe S, Swider M, Guzman JM, Boye SL, Hauswirth WW, Jacobson SG, Aguirre GD. 2014b. RPGR gene augmentation delivered at early, mid and late stage disease in a canine model of XLRP rescues photoreceptor function and structure. Association for Research in Vision & Ophthalmology, 4–8 May, E-abstract 3321, Orlando, FL.
19. Berendschot TT, DeLint PJ, van Norren D. 1996. Origin of tapetal-like reflexes in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 37: 2716–2723.
20. Boylan JP, Wright AF. 2000. Identification of a novel protein interacting with RPGR. Hum Mol Genet 9: 2085–2093.
21. Branham K, Othman M, Brumm M, Karoukis AJ, Atmaca Sonmez P, Yashar BM, Schwartz SB, Stover NB, Trzupek K, Wheaton D, et al. 2012. Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Invest Ophthalmol Vis Sci 53: 8232–8237.
22. Breuer DK, Yashar BM, Filippova E, Hiriyanna S, Lyons RH, Mears AJ, Asaye B, Acar C, Vervoort R, Wright AF, et al. 2002. A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. Am J Hum Genet 70: 1545– 1554.
23. Brunner S, Skosyrski S, Kirschner-Schwabe R, Knobeloch KP, Neidhardt J, Feil S, Glaus E, Luhmann UF, Ruther K, Berger W. 2010. Cone versus rod disease in a mutant Rpgr mouse caused by different genetic backgrounds. Invest Ophthalmol Vis Sci 51: 1106–1115.
24. Bukowy-Bieryllo Z, Zietkiewicz E, Loges NT, Wittmer M, Geremek M, Olbrich H, Fliegauf M, Voelkel K, Rutkiewicz E, Rutland J, et al. 2013. RPGR mutations might cause reduced orientation of respiratory cilia. Pediatr Pulmonol 48: 352–363.
25. Chang B, Khanna H, Hawes N, Jimeno D, He S, Lillo C, Parapuram SK, Cheng H, Scott A, Hurd RE, et al. 2006. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum Mol Genet 15: 1847–1857.
26. Cideciyan AV, Jacobson SG. 1994. Image analysis of the tapetal-like reflex in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 35: 3812–3824.
27. Cideciyan AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S, Roman AJ, Olivares MB, Schwartz SB, Komaromy AM, et al. 2013. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci 110: E517–E525
28. Demirci FY, Rigatti BW, Wen G, Radak AL, Mah TS, Baic CL, Traboulsi EI, Alitalo T, Ramser J, Gorin MB. 2002. Xlinked cone-rod dystrophy (locus COD1): Identification of mutations in RPGR exon ORF15. Am J Hum Genet 70: 1049–1053.
29. Ebenezer ND, Michaelides M, Jenkins SA, Audo I, Webster AR, Cheetham ME, Stockman A, Maher ER, Ainsworth JR, Yates JR, et al. 2005. Identification of novel RPGR ORF15 mutations in X-linked progressive cone-rod dystrophy (XLCORD) families. Invest Ophthalmol Vis Sci 46: 1891–1898.
30. Fahim AT, Bowne SJ, Sullivan LS, Webb KD, Williams JT, Wheaton DK, Birch DG, Daiger SP. 2011. Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-Linked retinitis pigmentosa due to RPGR mutations. PLoS ONE 6: e23021.
31. Fishman GA. 1978. Retinitis pigmentosa. Genetic percentages. Arch Ophthalmol 96: 822–826.
32. Fishman GA, Grover S, Jacobson SG, Alexander KR, Derlacki DJ, Wu W, Buraczynska M, Swaroop A. 1998. X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60. Ophthalmology 105: 2286– 2296.
33. Flaxel CJ, Jay M, Thiselton DL, Nayudu M, Hardcastle AJ, Wright A, Bird AC. 1999. Difference between RP2 and RP3 phenotypes in X linked retinitis pigmentosa. Br J Ophthalmol 83: 1144–1148.
34. Gakovic M, Shu X, Kasioulis I, Carpanini S, Moraga I, Wright AF. 2011. The role of RPGR in cilia formation and actin stability. Hum Mol Genet 20: 4840–4850. doi: 10.1371/journal.pone/0085408.
35. Genini S, Beltran WA, Aguirre GD. 2013. Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration. PLoS ONE 8: e85408.
36. Ghosh AK, Murga-Zamalloa CA, Chan L, Hitchcock PF, Swaroop A, Khanna H. 2011. Human retinopathy-associated ciliary protein retinitis pigmentosa GTPase regulator mediates cilia-dependent vertebrate development. Hum Mol Genet 19: 90–98.
37. Guyon R, Pearce-Kelling SE, Zeiss CJ, Acland GM, Aguirre GD. 2007. Analysis of six candidate genes as potential modifiers of disease expression in canine XLPRA1, a model for human X-linked retinitis pigmentosa 3. Mol Vis 13: 1094–1105.
38. Hong DH, Pawlyk BS, Shang J, Sandberg MA, Berson EL, Li T. 2000. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci 97: 3649–3654.
39. Hong DH, Yue G, Adamian M, Li T. 2001. Retinitis pigmentosa GTPase regulator (RPGRr)-interacting protein is stably associated with the photoreceptor ciliary axoneme and anchors RPGR to the connecting cilium. J Biol Chem 276: 12091–12099.
40. Hong DH, Pawlyk B, Sokolov M, Strissel KJ, Yang J, Tulloch B, Wright AF, Arshavsky VY, Li T. 2003. RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Invest Ophthalmol Vis Sci 44: 2413–2421.
41. Hong DH, Pawlyk BS, Adamian M, Li T. 2004. Dominant, gain-of-function mutant produced by truncation of RPGR. Invest Ophthalmol Vis Sci 45: 36–41.
42. Hong DH, Pawlyk BS, Adamian M, Sandberg MA, Li T. 2005. A single, abbreviated RPGR-ORF15 variant reconstitutes RPGR function in vivo. Invest Ophthalmol Vis Sci 46: 435–441.
43. Huang WC, Wright AF, Roman AJ, Cideciyan AV, Manson FD, Gewaily DY, Schwartz SB, Sadigh S, Limberis MP, Bell P, et al. 2012. RPGR-associated retinal degeneration in human X-Linked RP and a murine model. Invest Ophthalmol Vis Sci 53: 5594–5608.
44. Iannaccone A, Breuer DK, Wang XF, Kuo SF, Normando EM, Filippova E, Baldi A, Hiriyanna S, MacDonald CB, Baldi F, et al. 2003. Clinical and immunohistochemical evidence for an X linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation. J Med Genet 40: e118.
45. Iannaccone A, Wang X, Jablonski MM, Kuo SF, Baldi A, Cosgrove D, Morton CC, Swaroop A. 2004. Increasing evidence for syndromic phenotypes associated with RPGR mutations. Am J Ophthalmol 137: 785–786.
46. Jacobson SG, Yagasaki K, Feuer WJ, Roman AJ. 1989. Interocular asymmetry of visual function in heterozygotes of X-linked retinitis pigmentosa. Exp Eye Res 48: 679–691.
47. Jacobson SG, Buraczynska M, Milam AH, Chen C, Jarvalainen M, Fujita R, Wu W, Huang Y, Cideciyan AV, Swaroop A. 1997. Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Invest Ophthalmol Vis Sci 38: 1983–1997.
48. Jay M. 1982. On the heredity of retinitis pigmentosa. Br J Ophthalmol 66: 405–416.
49. Jin ZB, Liu XQ, Hayakawa M, Murakami A, Nao-i N. 2006. Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: Identification of four mutations. Mol Vis 12: 1167–1174.
50. Keith CG, Denton MJ, Chen JD. 1991. Clinical variability in a family with X-linked retinal dystrophy and the locus at the RP3 site. Ophthalmic Paediatr Genet 12: 91–98.
51. Khanna H, Hurd TW, Lillo C, Shu X, Parapuram SK, He S, Akimoto M, Wright AF, Margolis B, Williams DS, et al. 2005. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. J Biol Chem 280: 33580–33587.
52. Khanna H, Davis EE, Murga-Zamalloa CA, Estrada-Cuzcano A, Lopez I, den Hollander AI, Zonneveld MN, Othman MI, Waseem N, Chakarova CF, et al. 2009. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat Genet 41: 739–745.
53. Koenekoop RK, Loyer M, Hand CK, Al Mahdi H, Dembinska O, Beneish R, Racine J, Rouleau GA. 2003. Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families. Am J Ophthalmol 136: 678–687.
54. Komaromy AM, Varner SE, de Juan E, Acland GM, Aguirre GD. 2006. Application of a new subretinal injection device in the dog. Cell Transplantation 15: 511–519.
55. Komaromy AM, Alexander JJ, Cooper AE, Chiodo VA, Acland GM, Hauswirth WW, Aguirre GD. 2008. Targeting gene expression to cones with human cone opsin promoters in recombinant AAV. Gene Ther 15: 1049–1055.
56. Linari M, Ueffing M, Manson F, Wright A, Meitinger T, Becker J. 1999. The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Proc Natl Acad Sci 96: 1315– 1320.
57. Lorenz B, Andrassi M, Kretschmann U. 2003. Phenotype in two families with RP3 associated with RPGR mutations. Ophthalmic Genet 24: 89–101.
58. Mavlyutov TA, Zhao H, Ferreira PA. 2002. Species-specific subcellular localization of RPGR and RPGRIP isoforms: Implications for the phenotypic variability of congenital retinopathies among species. Hum Mol Genet 11: 1899– 1907.
59. Mears AJ, Hiriyanna S, Vervoort R, Yashar B, Gieser L, Fahrner S, Daiger SP, Heckenlively JR, Sieving PA, Wright AF, et al. 2000. Remapping of the RP15 locus for X-linked cone-rod degeneration to Xp11.4-p21.1, and identification of a de novo insertion in the RPGR exon ORF15. Am J Hum Genet 67: 1000–1003.
60. Meindl A, Dry K, Herrmann K, Manson F, Ciccodicola A, Edgar A, Carvalho MR, Achatz H, Hellebrand H, Lennon A, et al. 1996. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat Genet 13: 35–42.
61. Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, Marlin S, Clement A, Geremek M, Delaisi B, Bridoux AM, et al. 2006. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet 43: 326–333.
62. Murga-Zamalloa CA, Atkins SJ, Peranen J, Swaroop A, Khanna H. 2010a. Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: Implications for cilia dysfunction and photoreceptor degeneration. Hum Mol Genet 19: 3591–3598.
63. Murga-Zamalloa CA, Desai NJ, Hildebrandt F, Khanna H. 2010b. Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas. Mol Vis 16: 1373– 1381.
64. Neidhardt J, Glaus E, Barthelmes D, Zeitz C, Fleischhauer J, Berger W. 2007. Identification and characterization of a novel RPGR isoform in human retina. Hum Mutat 28: 797–807.
65. Otto EA, Loeys B, Khanna H, Hellemans J, Sudbrak R, Fan S, Muerb U, O’Toole JF, Helou J, Attanasio M, et al. 2005. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat Genet 37: 282–288.
66. Pelletier V, Jambou M, Delphin N, Zinovieva E, Stum M, Gigarel N, Dollfus H, Hamel C, Toutain A, Dufier JL, et al. 2007. Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: Genotype-phenotype correlations and impact on genetic counseling. Hum Mutat 28: 81–91.
67. Petersen-Jones SM, Bartoe JT, Fischer AJ, Scott M, Boye SL, Chiodo V, Hauswirth WW. 2009. AAV retinal transduction in a large animal model species: Comparison of a self-complementary AAV2/5 with a single-stranded AAV2/5 vector. Mol Vis 15: 1835–1842.
68. Roepman R, van Duijnhoven G, Rosenberg T, Pinckers AJ, Bleeker-Wagemakers LM, Bergen AA, Post J, Beck A, Reinhardt R, Ropers HH, et al. 1996. Positional cloning of the gene for X-linked retinitis pigmentosa 3: Homology with the guanine-nucleotide-exchange factor RCC1. Hum Mol Genet 5: 1035–1041
69. Roepman R, Bernoud-Hubac N, Schick DE, Maugeri A, Berger W, Ropers HH, Cremers FP, Ferreira PA. 2000. The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors. Hum Mol Genet 9: 2095–2105.
70. Ruddle JB, Ebenezer ND, Kearns LS, Mulhall LE, Mackey DA, Hardcastle AJ. 2009. RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population. Br J Ophthalmol 93: 1151–1154.
71. Sandberg MA, Rosner B, Weigel-DiFranco C, Dryja TP, Berson EL. 2007. Disease course of patients with X-linked retinitis pigmentosa due to RPGR gene mutations. Invest Ophthalmol Vis Sci 48: 1298–1304.
72. Schmid F, Glaus E, Cremers FP, Kloeckener-Gruissem B, Berger W, Neidhardt J. 2010. Mutation- and tissue-specific alterations of RPGR transcripts. Invest Ophthalmol Vis Sci 51: 1628–1635.
73. Sharon D, Sandberg MA, Rabe VW, Stillberger M, Dryja TP, Berson EL. 2003. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet 73: 1131–1146.
74. Shu X, Fry AM, Tulloch B, Manson FD, Crabb JW, Khanna H, Faragher AJ, Lennon A, He S, Trojan P, et al. 2005. RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin. Hum Mol Genet 14: 1183–1197.
75. Shu X, Simpson JR, Hart AW, Zeng Z, Patnaik SR, Gautier P, Murdoch E, Tulloch B, Wright AF. 2012. Functional characterization of the human RPGR proximal promoter. Invest Ophthalmol Vis Sci 53: 3951–3958.
76. Strazzeri JM, Hunter JJ, Masella BD, Yin L, Fischer WS, Diloreto DA Jr, Libby RT, Williams DR, Merigan WH. 2014. Focal damage to macaque photoreceptors produces persistent visual loss. Exp Eye Res 119: 88–96.
77. Szamier RB, Berson EL. 1985. Retinal histopathology of a carrier of X-chromosome-linked retinitis pigmentosa. Ophthalmology 92: 271–278.
78. Tao W, Wen R, Goddard MB, Sherman SD, O’Rourke PJ, Stabila PF, Bell WJ, Dean BJ, Kauper KA, Budz VA, et al. 2002. Encapsulated cell based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Invest Ophthalmol Vis Sci 43: 3292–3298.
79. Thiadens AA, Soerjoesing GG, Florijn RJ, Tjiam AG, den Hollander AI, van den Born LI, Riemslag FC, Bergen AA, Klaver CC. 2011. Clinical course of cone dystrophy caused by mutations in the RPGR gene. Graefes Arch Clin Exp Ophthalmol 249: 1527–1535.
80. Thompson DA, Khan NW, Othman MI, Chang B, Jia L, Grahek G, Wu Z, Hiriyanna S, Nellissery J, Li T, et al. 2012. Rd9 is a naturally occurring mouse model of a common form of retinitis pigmentosa caused by mutations in RPGR-ORF15. PLoS ONE 7: e35865. doi: 10.1371/journal.pone/0035865.
81. Vajaranant TS, Seiple W, Szlyk JP, Fishman GA. 2002. Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of X-linked retinitis pigmentosa. Ophthalmology 109: 560–568.
82. van Dorp DB, Wright AF, Carothers AD, Bleeker-Wagemakers EM. 1992. A family with RP3 type of X-linked retinitis pigmentosa: An association with ciliary abnormalities. Hum Genet 88: 331–334.
83. Vervoort R, Lennon A, Bird AC, Tulloch B, Axton R, Miano MG, Meindl A, Meitinger T, Ciccodicola A, Wright AF. 2000. Mutational hot spot within a new RPGR exon in Xlinked retinitis pigmentosa. Nat Genet 25: 462–466.
84. Walia S, Fishman GA, Swaroop A, Branham KE, Lindeman M, Othman M, Weleber RG. 2008. Discordant phenotypes in fraternal twins having an identical mutation in exon ORF15 of the RPGR gene. Arch Ophthalmol 126: 379–384.
85. Weber M, Rabinowitz J, Provost N, Conrath H, Folliot S, Briot D, Cherel Y, Chenuaud P, Samulski J, Moullier P, et al. 2003. Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. Mol Ther 7: 774–781.
86. Weleber RG, Butler NS, Murphey WH, Sheffield VC, Stone EM. 1997. X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR. Arch Ophthalmol 115: 1429–1435.
87. ex1-19 variant leads to severe photoreceptor degeneration. Invest Ophthalmol Vis Sci 52: 5189–5201.
88. ORF15 connects to the usher protein network through direct interactions with multiple whirlin isoforms. Invest Ophthalmol Vis Sci 53: 1519–1529.
89. Yang Z, Peachey NS, Moshfeghi DM, Thirumalaichary S, Chorich L, Shugart YY, Fan K, Zhang K. 2002. Mutations in the RPGR gene cause X-linked cone dystrophy. Hum Mol Genet 11: 605–611.
90. Zahid S, Khan N, Branham K, Othman M, Karoukis AJ, Sharma N, Moncrief A, Mahmood MN, Sieving PA, Swaroop A, et al. 2013. Phenotypic conservation in patients with X-linked retinitis pigmentosa caused by RPGR mutations. JAMA Ophthalmol 131: 1016–1025.
91. Zeiss CJ, Acland GM, Aguirre GD. 1999. Retinal pathology of canine X-linked progressive retinal atrophy, the locus homologue of RP3. Invest Ophthalmol Vis Sci 40: 3292– 3304.
92. Zhang Q, Acland GM, Wu WX, Johnson JL, Pearce-Kelling SE, Tulloch B, Vervoort R, Wright AF, Aguirre GD. 2002. Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Hum Mol Genet 11: 993–1003.
93. Zito I, Downes SM, Patel RJ, Cheetham ME, Ebenezer ND, Jenkins SA, Bhattacharya SS, Webster AR, Holder GE, Bird AC, et al. 2003. RPGR mutation associated with retinitis pigmentosa, impaired hearing, and sinorespiratory infections. J Med Genet 40: 609–615.