OMIA 000831-9615 : Progressive retinal atrophy, X-linked, type 1 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 300029 (trait) , 312610 (gene) , 304020 (trait) , 300834 (trait) , 300455 (trait)

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.

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

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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

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.
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.

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 05 Aug 2016
  • Changed by Frank Nicholas on 21 Jan 2018
  • Changed by Frank Nicholas on 18 Mar 2020
  • Changed by Imke Tammen2 on 22 Aug 2021