OMIA:001346-9615 : Progressive retinal atrophy, autosomal dominant in Canis lupus familiaris
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610445 (trait) , 613731 (trait) , 136880 (trait) , 180380 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
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. (2011)
Species-specific symbol: ADPRA
Molecular basis: Kijas et al. (2002) discovered an autosomal-dominant progressive retinal atrophy in English Mastiff dogs, with clinical signs very similar to a human dominant retinitis pigmentosa that is due to mutations in the gene for rhodopsin. Taking the rhodopsin gene as a strong comparative candidate, Kijas et al. (2002) sequenced all five exons of the canine rhodopsin gene from a heterozygous affected dog, and discovered a missense mutation (C-to-G transversion) at nucleotide 11, giving rise to a Thr-to-Arg amino acid substitution at position 4 of the peptide (T4R), in the extracellular domain. Noting that the mutation generates a BsmFI restriction fragment length polymorphism, Kijas et al. genotyped 26 affected and 21 related normal English Mastiffs. Three of the affected dogs were homozygous for the mutant allele; the rest were heterozygous. All related normal dogs were homozygous for the normal allele, as were 156 normal dogs from 17 other dog breeds [Frank Nicholas, 26 June 2002]
Kijas et al. (2003) noted that "Testing of PRA-affected animals from [other] 16 breeds revealed that none carry the T4R mutation, indicating a different cause of PRA".
Clinical features: As detailed by Kijas et al. (2002), rod vision is normal for at least the first few months. But by 12-18 months, degeneration is evident, spreading slowly from a disease focus in one retinal region. In addition, there is an abnormally slow recovery of rod photoreceptor function after exposure to light.Homozygotes have more severe clinical signs than heterozygotes [Frank Nicholas, 26 June 2002]
Iwabe et al. (2016) reported that "a short single exposure to a dose of white light that is not retinotoxic in [wild-type] WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors."
Breeds: Bull Mastiff, English Mastiff.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RHO||rhodopsin||Canis lupus familiaris||20||NC_051824.1 (5667219..5661948)||RHO||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|
|29||English Mastiff||Autosomal dominant PRA||RHO||missense||Naturally occurring variant||CanFam3.1||20||g.5637394G>C||c.11C>G||p.(T4R)||2002||11972042||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2022||Ji, R.L., Tao, Y.X. :|
|Mutations in rhodopsin, endothelin B receptor, and CC chemokine receptor 5 in large animals: Modeling human diseases. Prog Mol Biol Transl Sci 189:155-178, 2022. Pubmed reference: 35595348 . DOI: 10.1016/bs.pmbts.2022.02.003.|
|2018||Cideciyan, A.V., Sudharsan, R., Dufour, V.L., Massengill, M.T., Iwabe, S., Swider, M., Lisi, B., Sumaroka, A., Marinho, L.F., Appelbaum, T., Rossmiller, B., Hauswirth, W.W., Jacobson, S.G., Lewin, A.S., Aguirre, G.D., Beltran, W.A. :|
|Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector. Proc Natl Acad Sci U S A 115:E8547-E8556, 2018. Pubmed reference: 30127005 . DOI: 10.1073/pnas.1805055115.|
|2017||Sudharsan, R., Simone, K.M., Anderson, N.P., Aguirre, G.D., Beltran, W.A. :|
|Acute and protracted cell death in light-induced retinal degeneration in the canine model of rhodopsin autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 58:270-281, 2017. Pubmed reference: 28114588 . DOI: 10.1167/iovs.16-20749.|
|2016||Iwabe, S., Ying, G.S., Aguirre, G.D., Beltran, W.A. :|
|Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog. Exp Eye Res 146:341-353, 2016. Pubmed reference: 27085210 . DOI: 10.1016/j.exer.2016.04.006.|
|Palanova, A. :|
|The genetics of inherited retinal disorders in dogs: implications for diagnosis and management. Vet Med (Auckl) 7:41-51, 2016. Pubmed reference: 30050836 . DOI: 10.2147/VMRR.S63537.|
|2015||Marsili, S., Genini, S., Sudharsan, R., Gingrich, J., Aguirre, G.D., Beltran, W.A. :|
|Exclusion of the unfolded protein response in light-induced retinal degeneration in the canine T4R RHO model of autosomal dominant retinitis pigmentosa. PLoS One 10:e0115723, 2015. Pubmed reference: 25695253 . DOI: 10.1371/journal.pone.0115723.|
|2009||Gu, D., Beltran, WA., Pearce-Kelling, S., Li, Z., Acland, GM., Aguirre, GD. :|
|Steroids do not prevent photoreceptor degeneration in the light-exposed T4R rhodopsin mutant dog retina irrespective of AP-1 inhibition. Invest Ophthalmol Vis Sci 50:3482-94, 2009. Pubmed reference: 19234347 . DOI: 10.1167/iovs.08-3111.|
|2005||Cideciyan, AV., Jacobson, SG., Aleman, TS., Gu, D., Pearce-Kelling, SE., Sumaroka, A., Acland, GM., Aguirre, GD. :|
|In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa. Proc Natl Acad Sci U S A 102:5233-8, 2005. Pubmed reference: 9618546 .|
|Weinkle, TK., Center, SA., Randolph, JF., Warner, KL., Barr, SC., Erb, HN. :|
|Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002). J Am Vet Med Assoc 226:1869-80, 2005. Pubmed reference: 15934255 .|
|2004||Zhu, L., Jang, G.F., Jastrzebska, B., Filipek, S., Pearce-Kelling, S.E., Aguirre, G.D., Stenkamp, R.E., Acland, G.M., Palczewski, K. :|
|A naturally occurring mutation of the opsin gene (T4R) in dogs affects glycosylation and stability of the G protein-coupled receptor. J Biol Chem 279:53828-39, 2004. Pubmed reference: 15459196 . DOI: 10.1074/jbc.M408472200.|
|2003||Kijas, JW., Miller, BJ., Pearce-Kelling, SE., Aguirre, GD., Acland, GM. :|
|Canine models of ocular disease: outcross breedings define a dominant disorder present in the English mastiff and bull mastiff dog breeds. J Hered 94:27-30, 2003. Pubmed reference: 12692159 .|
|2002||Kijas, J.W., Cideciyan, A.V., Aleman, T.S., Pianta, M.J., Pearce-Kelling, S.E., Miller, B.J., Jacobson, S.G., Aguirre, G.D., Acland, G.M. :|
|Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa Proceedings of the National Academy of Sciences of the United States of America 99:6328-6333, 2002. Pubmed reference: 11972042 . DOI: 10.1073/pnas.082714499.|
- Created by Frank Nicholas on 15 Nov 2005
- Changed by Frank Nicholas on 02 Dec 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 20 Sep 2012
- Changed by Frank Nicholas on 05 Aug 2013
- Changed by Frank Nicholas on 26 Apr 2016
- Changed by Imke Tammen2 on 18 Jan 2023