OMIA:000831-9615 : Progressive retinal atrophy, X-linked, type 1 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: XLPRA1
Species-specific description: The difference between XLPRA1 (this entry) and XLPRA2 (OMIA 001518-9615) 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 "five-nucleotide deletion (delGAGAA) between 1028 and 1032" in the canine RPGR gene as a causal mutation for a form of X-linked PRA they call XPRA1. The authors also noted that "The XLPRA1 mutation causes a frameshift and immediate premature stop; the truncated protein is missing 230 C-terminal amino acids, causing a slight decrease in the isoelectric point (3.89 versus 4.01 in normal). By mutation scanning, we also found the same five-nucleotide deletion in the Samoyed breed with a clinically similar X-linked retinal degeneration (data not shown)"
Kropatsch et al. (2016): "Whole exome sequencing in two PRA-affected Weimaraner dogs identified a large deletion [maximum size 5,006 bp] comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene".
Pathology: As summarised by Zeiss et al. (1999): " The earliest lesion detectable by electron microscopy was vesiculation of rod discs, followed by disruption of outer segments and death of rods. Loss of cones and progressive atrophy of inner retinal layers followed. Lesions were most severe in the peripheral retina and advanced toward the optic disc with disease progression. Significant variation in disease severity was present in males despite the presence of the same disease allele in all affected dogs." As concluded by the same authors: "X-linked retinal degeneration is characterized by initial degeneration of rod photoreceptors, followed by loss of cones and progressive atrophy of the inner retina. Carrier females display a phenotype consistent with random X-chromosome inactivation. Variation in genetic background may alter expression of the disease allele in affected animals, thus accounting for variation in phenotypic expression of the disease."
Breeds: Samoyed, Siberian Husky, Weimaraner.
|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|
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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|
|688||Weimaraner||Progressive retinal atrophy, X-linked, type 1||RPGR||deletion, gross (>20)||Naturally occurring variant||X||"a large deletion [maximum size 5,006 bp] comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene"||2016||27398221|
|480||Samoyed Siberian Husky||Progressive retinal atrophy, X-linked, type 1||RPGR||deletion, small (<=20)||Naturally occurring variant||ROS_Cfam_1.0||X||g.33126490_33126494del||c.3416_3420del||p.(R1139Ifs*2)||published as a "five-nucleotide deletion (delGAGAA) between 1028 and 1032" in exon ORF15 of the canine RPGR gene [GenBank accession no. AF385629]; updated c.DNA and protein positions kindly provided by Leonardo Murgiano [15/2/20022]||2002||11978759|
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.|
|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.|
|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.|
|2016||Appelbaum, T., Becker, D., Santana, E., Aguirre, G.D. :|
|Molecular studies of phenotype variation in canine RPGR-XLPRA1. Mol Vis 22:319-31, 2016. Pubmed reference: 27122963 .|
|Kropatsch, R., Akkad, D.A., Frank, M., Rosenhagen, C., Altmüller, J., Nürnberg, P., Epplen, J.T., Dekomien, G. :|
|A large deletion in RPGR causes XLPRA in Weimaraner dogs. Canine Genet Epidemiol 3:7, 2016. Pubmed reference: 27398221 . DOI: 10.1186/s40575-016-0037-x.|
|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.|
|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.|
|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||Beltran, WA., Wen, R., Acland, GM., Aguirre, GD. :|
|Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina. Exp Eye Res 84:753-71, 2007. Pubmed reference: 17320077 . DOI: 10.1016/j.exer.2006.12.019.|
|Guyon, R., Pearce-Kelling, SE., Zeiss, CJ., Acland, GM., Aguirre, GD. :|
|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 13:1094-105, 2007. Pubmed reference: 17653054 .|
|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.|
|2002||Zangerl, B., Zhang, Q., Acland, G.M., Aguirre, G.D. :|
|Characterization of three microsatellite loci linked to the canine RP3 interval. J Hered 93:70-3, 2002. Pubmed reference: 12011183 .|
|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 .|
|2001||Zhang, Q., Acland, G.M., Zangerl, B., Johnson, J.L., Mao, Z., Zeiss, C.J., Ostrander, E.A., Aguirre, G.D. :|
|Fine mapping of canine XLPRA establishes homology of the human and canine RP3 intervals. Invest Ophthalmol Vis Sci 42:2466-71, 2001. Pubmed reference: 11581184 .|
|2000||Zeiss, C.J., Ray, K., Acland, G.M., Aguirre, G.D. :|
|Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3) Human Molecular Genetics 9:531-537, 2000. Pubmed reference: 10699176 .|
|Zhang, Q., Ray, K., Acland, G.M., Czarnecki, J.M., Aguirre, G.D. :|
|Molecular cloning, characterization and expression of a novel retinal clusterin-like protein cDNA. Gene 243:151-60, 2000. Pubmed reference: 10675623 .|
|1999||Zeiss, G.J., Acland, G.M., Aguirre, G.D. :|
|Retinal pathology of canine X-linked progressive retinal atrophy, the locus homologue of RP3 Investigative Ophthalmology & Visual Science 40:3292-3304, 1999. Pubmed reference: 10586956 .|
|1994||Acland, G.M., Blanton, S.H., Hershfield, B., Aguirre, G.D. :|
|Animal model: XLPRA: A canine retinal degeneration inherited as an X-linked trait American Journal of Medical Genetics 52:27-33, 1994. Pubmed reference: 7977457 . DOI: 10.1002/ajmg.1320520106.|
|1980||Dice, P.F. :|
|Progressive retinal atrophy in the Samoyed. Mod Vet Pract 61:59-60, 1980. Pubmed reference: 7366567 .|
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