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

Possibly relevant human trait(s) and/or gene(s) (MIM number): 300029

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

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".

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_006621.3 (33105036..33056371) 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Weimaraner Progressive retinal atrophy, X-linked, type 1 RPGR deletion, gross (>20) "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
Samoyed Siberian Husky Progressive retinal atrophy, X-linked, type 1 RPGR deletion, small (<=20) c.1028_1032delGAGAA a "five-nucleotide deletion (delGAGAA) between 1028 and 1032" in the canine RPGR gene 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.
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.
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.
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