OMIA:001518-9615 : Progressive retinal atrophy, X-linked, type 2 in Canis lupus familiaris |
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 300029 (trait) , 312610 (gene) , 304020 (trait) , 300834 (trait) , 300455 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: X-linked
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2002
Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)
Species-specific symbol: XLPRA2
Species-specific description: The difference between XLPRA1 (OMIA 000831-9615) and XLPRA2 (this entry) is summarised by Appelbaum et al. (2020) as "XLPRA1-affected dogs have normal PR morphogenesis, after which progressive rod–cone degeneration develops in the peripheral retina, gradually advancing toward the optic disc. . . . The phenotype associated with XLPRA2 is very severe and manifests during early retinal development."
Molecular basis: Based on a comparative positional cloning approach (the canine disorder maps to a location on the canine X chromosome that is homologous with the location of the same disorder (RP3) in humans, which is due to mutations in the RPGR gene), Zhang et al. (2002) identified a "a two-nucleotide deletion (delGA) in 1084–1085" in the canine RPGR gene as a causal mutation for a form of X-linked PRA they call XPRA2. The authors noted that this deletion "results in a frameshift that significantly changes the deduced peptide sequence, causing an increased isoelectric point (4.30 versus 4.01), and leads to the inclusion of 34 additional basic residues before prematurely terminating translation 71 amino acids downstream".
Clinical features: Beltran et al. (2006): "Abnormal development of photoreceptors was recognizable as early as 3.9 weeks of age. Outer segment (OS) misalignment was followed by their disorganization and fragmentation. Reduction in length and broadening of rod and cone inner segments (IS) was next observed, followed by the focal loss of rod and cone IS at later time points. The proportion of dying photoreceptors peaked at approximately 6 to 7 weeks of age and was significantly reduced after 12 weeks. In addition to rod and cone opsin mislocalization, there was early rod neurite sprouting, retraction of rod bipolar cell dendrites, and increased Müller cell reactivity. Later in the course of the disease, changes were also noted in horizontal cells and amacrine cells." As summarised by these authors: "XLPRA2 is an early-onset model of XLRP that is morphologically characterized by abnormal photoreceptor maturation followed by progressive rod-cone degeneration and early inner retina remodeling. "
Breed: Mongrel.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| RPGR | retinitis pigmentosa GTPase regulator | Canis lupus familiaris | X | NC_051843.1 (33156658..33082215) | RPGR | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 481 | Mongrel | Progressive retinal atrophy, X-linked, type 2 | RPGR | deletion, small (<=20) | Naturally occurring variant | ROS_Cfam_1.0 | X | g.33126437_33126438del | c.3472_3473del | p.E1158Gfs*212 | published as "a two-nucleotide deletion (delGA) in c.1084-1085" [GenBank accession no. AF385629] in the exon ORF15 of the canine RPGR gene; updated c.DNA and protein positions kindly provided by Leonardo Murgiano [15/2/20022] | 2002 | 11978759 |
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Awadh Hashem, S., Georgiou, M., Ali, R.R., Michaelides, M. : |
| RPGR-related retinopathy: clinical features, molecular genetics, and gene replacement therapy. Cold Spring Harb Perspect Med :, 2023. Pubmed reference: 37188525 . DOI: 10.1101/cshperspect.a041280. | |
| 2022 | Badiei, A., Beltran, W.A., Aguirre, G.D. : |
| Altered transsulfuration pathway enzymes and redox homeostasis in inherited retinal degenerative diseases. Exp Eye Res 215:108902, 2022. Pubmed reference: 34954206 . DOI: 10.1016/j.exer.2021.108902. | |
| 2021 | Sudharsan, R., Murgiano, L., Tang, H.Y., Olsen, T.W., Chavali, V.R.M., Aguirre, G.D., Beltran, W.A. : |
| Short prolactin isoforms are expressed in photoreceptors of canine retinas undergoing retinal degeneration. Sci Rep 11:460, 2021. Pubmed reference: 33432105 . DOI: 10.1038/s41598-020-80691-6. | |
| 2020 | Appelbaum, T., Santana, E., Aguirre, G.D. : |
| Critical decrease in the level of axon guidance receptor ROBO1 in rod synaptic terminals is followed by axon retraction. Invest Ophthalmol Vis Sci 61:11, 2020. Pubmed reference: 32176262 . DOI: 10.1167/iovs.61.3.11. | |
| Dufour, V.L.L., Cideciyan, A.V., Ye, G.J., Song, C., Timmers, A., Habecker, P., Pan, W., Weinstein, N., Swider, M., Durham, A., Ying, G.S., Robinson, P., Jacobson, S., Knop, D.R., Chulay, J.D., Shearman, M.S., Aguirre, G., Beltran, W. : | |
| Toxicity and efficacy evaluation of an AAV vector expressing codon-optimized RPGR delivered by subretinal injection in a canine model of X-linked retinitis pigmentosa. Hum Gene Ther 31:253-267, 2020. Pubmed reference: 31910043 . DOI: 10.1089/hum.2019.297. | |
| Song, C., Dufour, V.L., Cideciyan, A.V., Ye, G.J., Swider, M., Newmark, J.A., Timmers, A.M., Robinson, P.M., Knop, D.R., Chulay, J.D., Jacobson, S.G., Aguirre, G.D., Beltran, W.A., Shearman, M.S. : | |
| Dose range finding studies with two RPGR transgenes in a canine model of X-linked retinitis pigmentosa treated with subretinal gene therapy. Hum Gene Ther 31:743-755, 2020. Pubmed reference: 32414297 . DOI: 10.1089/hum.2019.337. | |
| Switonski, M. : | |
| Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222 . DOI: 10.1007/s13353-020-00554-8. | |
| 2017 | Beltran, W.A., Cideciyan, A.V., Boye, S.E., Ye, G.J., Iwabe, S., Dufour, V.L., Marinho, L.F., Swider, M., Kosyk, M.S., Sha, J., Boye, S.L., Peterson, J.J., Witherspoon, C.D., Alexander, J.J., Ying, G.S., Shearman, M.S., Chulay, J.D., Hauswirth, W.W., Gamlin, P.D., Jacobson, S.G., Aguirre, G.D. : |
| Optimization of retinal gene therapy for X-linked retinitis pigmentosa due to RPGR mutations. Mol Ther 25:1866-1880, 2017. Pubmed reference: 28566226 . DOI: 10.1016/j.ymthe.2017.05.004. | |
| Sudharsan, R., Beiting, D.P., Aguirre, G.D., Beltran, W.A. : | |
| Involvement of innate immune system in late stages of inherited photoreceptor degeneration. Sci Rep 7:17897, 2017. Pubmed reference: 29263354 . DOI: 10.1038/s41598-017-18236-7. | |
| 2015 | Beltran, W.A., Cideciyan, A.V., Iwabe, S., Swider, M., Kosyk, M.S., McDaid, K., Martynyuk, I., Ying, G.S., Shaffer, J., Deng, W.T., Boye, S.L., Lewin, A.S., Hauswirth, W.W., Jacobson, S.G., Aguirre, G.D. : |
| Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease. Proc Natl Acad Sci U S A 112:E5844-53, 2015. Pubmed reference: 26460017 . DOI: 10.1073/pnas.1509914112. | |
| 2014 | Beltran, W.A., Cideciyan, A.V., Guziewicz, K.E., Iwabe, S., Swider, M., Scott, E.M., Savina, S.V., Ruthel, G., Stefano, F., Zhang, L., Zorger, R., Sumaroka, A., Jacobson, S.G., Aguirre, G.D. : |
| Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations. PLoS One 9:e90390, 2014. Pubmed reference: 24599007 . DOI: 10.1371/journal.pone.0090390. | |
| Genini, S., Guziewicz, K.E., Beltran, W.A., Aguirre, G.D. : | |
| Altered miRNA expression in canine retinas during normal development and in models of retinal degeneration. BMC Genomics 15:172, 2014. Pubmed reference: 24581223 . DOI: 10.1186/1471-2164-15-172. | |
| 2013 | Genini, S., Beltran, W.A., Aguirre, G.D. : |
| Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration. PLoS One 8:e85408, 2013. Pubmed reference: 24367709 . DOI: 10.1371/journal.pone.0085408. | |
| 2012 | Beltran, W.A., Cideciyan, A.V., Lewin, A.S., Iwabe, S., Khanna, H., Sumaroka, A., Chiodo, V.A., Fajardo, D.S., Román, A.J., Deng, W.T., Swider, M., Alemán, T.S., Boye, S.L., Genini, S., Swaroop, A., Hauswirth, W.W., Jacobson, S.G., Aguirre, G.D. : |
| Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci U S A 109:2132-7, 2012. Pubmed reference: 22308428 . DOI: 10.1073/pnas.1118847109. | |
| Miyadera, K., Acland, G.M., Aguirre, G.D. : | |
| Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099 . DOI: 10.1007/s00335-011-9361-3. | |
| 2010 | Genini, S., Zangerl, B., Slavik, J., Acland, GM., Beltran, WA., Aguirre, GD. : |
| Transcriptional Profile Analysis of RPGRORF15 Frameshift Mutation Identifies Novel Genes Associated with Retinal Degeneration. Invest Ophthalmol Vis Sci 51:6038-50, 2010. Pubmed reference: 20574030 . DOI: 10.1167/iovs.10-5443. | |
| 2009 | Beltran, W.A., Acland, G.M., Aguirre, G.D. : |
| Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations. Invest Ophthalmol Vis Sci 50:3985-95, 2009. Pubmed reference: 19255154 . DOI: 10.1167/iovs.08-3364. | |
| 2007 | Zangerl, B., Johnson, J.L., Acland, G.M., Aguirre, G.D. : |
| Independent origin and restricted distribution of RPGR deletions causing XLPRA. J Hered 98:526-30, 2007. Pubmed reference: 17646274 . DOI: 10.1093/jhered/esm060. | |
| 2006 | Beltran, WA., Hammond, P., Acland, GM., Aguirre, GD. : |
| 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 47:1669-81, 2006. Pubmed reference: 16565408 . DOI: 10.1167/iovs.05-0845. | |
| 2002 | Zhang, Q., Acland, GM., Wu, WX., Johnson, JL., Pearce-Kelling, S., Tulloch, B., Vervoort, R., Wright, AF., Aguirre, GD. : |
| Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Hum Mol Genet 11:993-1003, 2002. Pubmed reference: 11978759 . |
Edit History
- Created by Frank Nicholas on 02 Nov 2010
- Changed by Frank Nicholas on 02 Dec 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 21 Sep 2012
- Changed by Frank Nicholas on 18 Mar 2020
- Changed by Imke Tammen2 on 22 Aug 2021