OMIA:001298-9615 : Progressive rod-cone degeneration in Canis lupus familiaris (dog)

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610598 (gene) , 610599 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)

Species-specific symbol: prcd

Mapping: Using the power of comparative mapping, Acland et al. (1998) showed that this disorder in dogs maps to the same location as the gene for retinitis pigmentosa 17 in humans.

Molecular basis: Zangerl et al. (2006) identified a novel gene that they called PRCD in a 106kb candidate region on CFA9. They also showed that "a homozygous mutation (TGC>TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested".

Clinical features: Clinical features of the disease are a result of degeneration of the rods and cones in the eye (Spencer et al., 2016). Dogs are born with normal vision but in adolescence or early adulthood begin to show clinical signs (Miyadera, 2014). The disease typically manifests initially as a lack of coordination in dim light and night blindness (Miyadera, 2014). Affected dogs may also show an aversion to bright lights, difficulty navigating familiar areas and failure to focus on small objects such as balls or toys (Miyadera, 2014). As the cones of the eye degenerate, the night blindness will progress to day blindness (Miyadera, 2012). Ultimately, the disease results in total blindness (Miaydera, 2012). Currently, there is no known cure or treatment for slowing down progression of PRCD. Progression varies between individuals but most dogs become completely blind in 1 – 2 years (Zangerl et al., 2006). [IT thanks DVM student Lauren Alam, who provided the basis of this contribution in April 2022]

Pathology: The PRCD protein is bound to discs in the outer segments of rods and cones (Spencer et al., 2016; Allon et al., 2019). The PRCD protein is essential for long-term photoreceptor viability (Spencer et al., 2019). In PRCD disease, the protein is mislocalised from the outer segment discs (Spencer et al., 2016). In early disease about 40% reduction in rod disc renewal is seen, and the visual cells of the posterior pole and equatorial regions of the eye demonstrate vesicular appearances and outer segment lamellar disorientation (Aguirre et al., 1982; Spencer et al., 2019). As the disease progresses, all photoreceptor outer segments display changes including misoriented discs, subretinal invasion of phagocytic cells and extracellular vesicles (Spencer et al., 2019). Outer segments are eventually lost entirely (Spencer et al., 2019). [IT thanks DVM student Lauren Alam, who provided the basis of this contribution in April 2022]

Prevalence: Lewis and Mellersh (2019) reported a decline in frequency of the PRCD:c.5G>A variant in Labrador Retrievers from 0.078 (7.8%) prior to publication of the variant, to 0.003 (0.3%) 8-10 years after publication of the variant. This represents a 96.5% decline in frequency of the variant as a result of testing. For the same variant in English Cocker Spaniels, the equivalent results were a decline in frequency from 0.126 (12.6%) to 0.006 (0.6%) 8-10 years after publication of the variant, which represents a decline in frequency of 95.1% as a result of testing. Andrade et al. (2019) reported the frequency of this same variant in English Cocker Spaniels in Brazil: "220 ECS dogs was used for genotyping, of which 131 were registered from 18 different kennels and 89 were unregistered. . . . The . . .[PRCD:c.5G>A] allele frequency was 25.5%. Among the registered dogs, the allele frequency was 14.9%; among the dogs with no history of registration, the allele frequency was 41%." Clark et al. (2023) "utilized a large set of genotypes from dogs tested for the progressive rod-cone degeneration–progressive retinal atrophy (prcd-PRA) G>A missense PRCD variant (n = 86,667) and the collie eye anomaly (CEA)-associated NHEJ1 deletion (n = 33,834) ... . ... Forty-one breeds and breed mixes in our prcd-PRA dataset were genotyped for having at least one copy of the PRCD variant ... . Regression modeling showed time progression to significantly affect the odds of a dog being homozygous or heterozygous for either disease, as do variables including breed and breed popularity. This study shows that genetic testing informed breeding decisions to produce fewer affected dogs. However, the presence of dogs homozygous for the disease variant, especially for prcd-PRA, was still observed fourteen years after test availability, potentially due to crosses of unknown carriers."

Breeds: American Cocker Spaniel (Dog) (VBO_0200038), American Eskimo Dog (Dog) (VBO_0200046), Australian Cattle Dog (Dog) (VBO_0200088), Australian Shepherd (Dog) (VBO_0200095), Australian Stumpy Tail Cattle Dog (Dog) (VBO_0200097), Barbet (Dog) (VBO_0200119), Chesapeake Bay Retriever (Dog) (VBO_0200326), Chinese Crested (Dog) (VBO_0200345), Cockapoo (Dog) (VBO_0200370), English Cocker Spaniel (Dog) (VBO_0200486), Entlebucher Mountain Dog (Dog) (VBO_0200503), Finnish Lapphund (Dog) (VBO_0200523), Golden Retriever (Dog) (VBO_0200610), Goldendoodle (Dog) (VBO_0200611), Karelian Bear Dog (Dog) (VBO_0200754), Kuvasz (Dog) (VBO_0200793), Labradoodle (Dog) (VBO_0200798), Labrador Retriever (Dog) (VBO_0200800), Lapponian Herder (Dog) (VBO_0200814), Norwegian Elkhound (Dog) (VBO_0200955), Nova Scotia Duck Tolling Retriever (Dog) (VBO_0200964), Poodle (Dog) (VBO_0201048), Poodle, Miniature (Dog) (VBO_0201051), Poodle, Toy (Dog) (VBO_0201061), Portuguese Podengo (Dog) (VBO_0201067), Portuguese Water Dog (Dog) (VBO_0201077), Schipperke (Dog) (VBO_0201184), Silky Terrier (Dog) (VBO_0201237), Spanish Water Dog (Dog) (VBO_0201280), Swedish Lapphund (Dog) (VBO_0201315), Swedish White Elkhound (Dog) (VBO_0201317), Yorkshire Terrier (Dog) (VBO_0201448).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PRCD progressive rod-cone degeneration Canis lupus familiaris 9 NC_051813.1 (4868644..4855717) PRCD 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 Year Published PubMed ID(s) Acknowledgements
76 American Cocker Spaniel (Dog) Australian Cattle Dog (Dog) Australian Shepherd (Dog) Australian Stumpy Tail Cattle Dog (Dog) Chesapeake Bay Retriever (Dog) Chinese Crested (Dog) English Cocker Spaniel (Dog) Entlebucher Mountain Dog (Dog) Finnish Lapphund (Dog) Golden Retriever (Dog) Karelian Bear Dog (Dog) Kuvasz (Dog) Labrador Retriever (Dog) Lapponian Herder (Dog) Norwegian Elkhound (Dog) Nova Scotia Duck Tolling Retriever (Dog) Poodle, Miniature (Dog) Poodle, Toy (Dog) Portuguese Podengo (Dog) Portuguese Water Dog (Dog) Spanish Water Dog (Dog) Swedish Lapphund (Dog) Swedish White Elkhound (Dog) Yorkshire Terrier (Dog) Progressive rod-cone degeneration PRCD missense Naturally occurring variant CanFam3.1 9 g.4188663C>T c.5G>A p.(C2Y) ENSCAFT00845030294.1; ENSCAFP00845023755.1; ROS_Cfam_1.0:g.4864649C>T; Portuguese Podengo and Swedish White Elkhound were reported in PMID: 37582787 rs852451717 2006 16938425 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001298-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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 Arizmendi, A., Rudd Garces, G., Crespi, J.A., Olivera, L.H., Barrientos, L.S., Peral García, P., Giovambattista, G. :
Analysis of Doberman Pinscher and Toy Poodle samples with targeted next-generation sequencing. Gene 853:147069, 2023. Pubmed reference: 36427679. DOI: 10.1016/j.gene.2022.147069.
Clark, J.A., Anderson, H., Donner, J., Pearce-Kelling, S., Ekenstedt, K.J. :
Global frequency analyses of canine progressive rod-cone degeneration-progressive retinal atrophy and Collie eye anomaly using commercial genetic testing data. Genes (Basel) 14:2093, 2023. Pubmed reference: 38003037. DOI: 10.3390/genes14112093.
Ghilardi, S., Bagardi, M., Frattini, S., Barbariga, G.E., Brambilla, P.G., Minozzi, G., Polli, M. :
Genotypic and allelic frequencies of progressive rod-cone degeneration and other main variants associated with progressive retinal atrophy in Italian dogs. Vet Rec Open 10:e77, 2023. Pubmed reference: 38028226. DOI: 10.1002/vro2.77.
Majchrakova, Z., Hrckova Turnova, E., Bielikova, M., Turna, J., Dudas, A. :
The incidence of genetic disease alleles in Australian Shepherd dog breed in European countries. PLoS One 18:e0281215, 2023. Pubmed reference: 36848350. DOI: 10.1371/journal.pone.0281215.
Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
Motipally, S.I., Kolandaivelu, S. :
Absence of PRCD leads to dysregulation in lipid homeostasis resulting in disorganization of photoreceptor outer segment structure. Adv Exp Med Biol 1415:389-394, 2023. Pubmed reference: 37440062. DOI: 10.1007/978-3-031-27681-1_57.
2022 Park, S.A., Rhodes, J., Iwabe, S., Ying, G.S., Pan, W., Huang, J., Komáromy, A.M. :
Quantitative and qualitative characterization of retinal dystrophies in canine models of inherited retinal diseases using spectral domain optical coherence tomography (SD-OCT). Exp Eye Res :109106, 2022. Pubmed reference: 35588783. DOI: 10.1016/j.exer.2022.109106.
Trecenti-Santana, A.S., Guiraldelli, G.G., Albertino, L.G., Ferreira, J.F., Andrade, F.M., Borges, A.S., Oliveira-Filho, J.P. :
Allele frequency of SLC4A3 (PRA1), TTC8 (PRA2), and PRA-prcd mutations in golden retrievers in Brazil. Front Vet Sci 9:973854, 2022. Pubmed reference: 36325094. DOI: 10.3389/fvets.2022.973854.
2021 Genetics Committee of the American College of Veterinary Opthalmologists :
The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf , 2021.
2019 Allon, G., Mann, I., Remez, L., Sehn, E., Rizel, L., Nevet, M.J., Perlman, I., Wolfrum, U., Ben-Yosef, T. :
PRCD is concentrated at the base of photoreceptor outer segments and is involved in outer segment disc formation. Hum Mol Genet 28:4078-4088, 2019. Pubmed reference: 31628458. DOI: 10.1093/hmg/ddz248.
Andrade, L.R., Caceres, A.M., Trecenti, A.S., Brandão, C.V.S., Gandolfi, M.G., Aguiar, E.V., Andrade, D.G.A., Borges, A.S., Oliveira-Filho, J.P. :
Allele frequency of the c.5G>A mutation in the PRCD gene responsible for progressive retinal atrophy in English Cocker Spaniel dogs. Animals (Basel) 9:844, 2019. Pubmed reference: 31640229. DOI: 10.3390/ani9100844.
Lewis, T.W., Mellersh, C.S. :
Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.
Spencer, W.J., Arshavsky, V.Y. :
PRCD is a small disc-specific rhodopsin-binding protein of unknown function. Adv Exp Med Biol 1185:531-535, 2019. Pubmed reference: 31884666. DOI: 10.1007/978-3-030-27378-1_87.
Spencer, W.J., Ding, J.D., Lewis, T.R., Yu, C., Phan, S., Pearring, J.N., Kim, K.Y., Thor, A., Mathew, R., Kalnitsky, J., Hao, Y., Travis, A.M., Biswas, S.K., Lo, W.K., Besharse, J.C., Ellisman, M.H., Saban, D.R., Burns, M.E., Arshavsky, V.Y. :
PRCD is essential for high-fidelity photoreceptor disc formation. Proc Natl Acad Sci U S A 116:13087-13096, 2019. Pubmed reference: 31189593. DOI: 10.1073/pnas.1906421116.
2017 Takanosu, M. :
Different allelic frequency of progressive rod-cone degeneration in two populations of Labrador Retrievers in Japan. J Vet Med Sci 79:1746-1748, 2017. Pubmed reference: 28855430. DOI: 10.1292/jvms.17-0243.
2016 Kohyama, M., Tada, N., Mitsui, H., Tomioka, H., Tsutsui, T., Yabuki, A., Rahman, M.M., Kushida, K., Mizukami, K., Yamato, O. :
Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan. J Vet Med Sci 78:481-4, 2016. Pubmed reference: 26549343. DOI: 10.1292/jvms.15-0279.
Spencer, W.J., Pearring, J.N., Salinas, R.Y., Loiselle, D.R., Skiba, N.P., Arshavsky, V.Y. :
Progressive rod-cone degeneration (PRCD) protein requires N-terminal S-acylation and rhodopsin binding for photoreceptor outer segment localization and maintaining intracellular stability. Biochemistry 55:5028-5037, 2016. Pubmed reference: 27509380. DOI: 10.1021/acs.biochem.6b00489.
2014 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.
Miyadera, K. :
Inherited retinal diseases in dogs: advances in gene/mutation discovery. Dobutsu Iden Ikushu Kenkyu 42:79-89, 2014. Pubmed reference: 26120276. DOI: 10.5924/abgri.42.79.
2012 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.
2011 Dostal, J., Palánová, A., Horak, P. :
Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression. Veterinární Medicína 56:243-247, 2011. DOI: 10.17221/1564-VETMED.
2009 Gentilini, F., Rovesti, GL., Turba, ME. :
Real-time detection of the mutation responsible for progressive rod-cone degeneration in Labrador Retriever dogs using locked nucleic acid TaqMan probes. J Vet Diagn Invest 21:689-92, 2009. Pubmed reference: 19737766.
2006 Goldstein, O., Zangerl, B., Pearce-Kelling, S., Sidjanin, D.J., Kijas, J.W., Felix, J., Acland, G.M., Aguirre, G.D. :
Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome. Genomics 88:541-50, 2006. Pubmed reference: 16859891. DOI: 10.1016/j.ygeno.2006.05.013.
Zangerl, B., Goldstein, O., Philp, AR., Lindauer, SJ., Pearce-Kelling, SE., Mullins, RF., Graphodatsky, AS., Ripoll, D., Felix, JS., Stone, EM., Acland, GM., Aguirre, GD. :
Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88:551-563, 2006. Pubmed reference: 16938425. DOI: 10.1016/j.ygeno.2006.07.007.
2003 Sidjanin, D.J., Miller, B., Kijas, J., McElwee, J., Pillardy, J., Malek, J., Pai, G., Feldblyum, T., Fraser, C., Acland, G., Aguirre, G. :
Radiation hybrid map, physical map, and low-pass genomic sequence of the canine prcd region on CFA9 and comparative mapping with the syntenic region on human chromosome 17. Genomics 81:138-48, 2003. Pubmed reference: 12620391.
1999 Gu, W.K., Ray, K., Pearce-Kelling, S., Baldwin, V.J., Langston, A.A., Ray, J., Ostrander, E.A., Acland, G.M., Aguirre, G.D. :
Evaluation of the APOH gene as a positional candidate for prcd in dogs Investigative Ophthalmology & Visual Science 40:1229-1237, 1999. Pubmed reference: 10235557.
1998 Acland, G.M., Ray, K., Mellersh, C.S., Gu, W.K., Langston, A.A., Rine, J., Ostrander, E.A., Aguirre, G.D. :
Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans Proceedings of the National Academy of Sciences of the United States of America 95:3048-3053, 1998. Pubmed reference: 9501213.
Anon. :
Researchers discover likely link between human, canine gene and blindness Journal of the American Veterinary Medical Association 212:1532, 1998. Pubmed reference: 9634355.
Gu, W.K., Acland, G.M., Langston, A.A., Ostrander, E.A., Aguirre, G.D., Ray, K. :
Identification of a RAPD marker linked to progressive rod-cone degeneration in dogs Mammalian Genome 9:740-744, 1998. Pubmed reference: 9716659.
Lin, C.T., Petersenjones, S.M., Sargan, D.R. :
Isolation and investigation of canine phosducin as a candidate for canine generalized progressive retinal atrophies Experimental Eye Research 67:473-480, 1998. Pubmed reference: 9820795. DOI: 10.1006/exer.1998.0569.
1997 Gould, D.J., Petersenjones, S.M., Lin, C.T., Sargan, D.R. :
Cloning of canine ROM-1 and its investigation as a candidate gene for generalized progressive retinal atrophies in dogs Animal Genetics 28:391-396, 1997. Pubmed reference: 9589581.
1996 Ray, K., Acland, G.M., Aguirre, G.D. :
Nonallelism of erd and prcd and exclusion of the canine rds peripherin gene as a candidate for both retinal degeneration loci Investigative Ophthalmology & Visual Science 37:783-794, 1996. Pubmed reference: 8603863.
1990 Acland, G.M., Halloranblanton, S., Boughman, J.A., Aguirre, G.D. :
Segregation distortion in inheritance of progressive rod cone degeneration (Prcd) in Miniature Poodle dogs. American Journal of Medical Genetics 35:354-359, 1990. Pubmed reference: 2309782. DOI: 10.1002/ajmg.1320350309.
1988 Aguirre, G.D., Acland, G.M. :
Variation in retinal degeneration phenotype inherited at the prcd locus Experimental Eye Research 46:663-387, 1988. Pubmed reference: 3164273.
1982 Aguirre, G., Alligood, J., O'Brien, P., Buyukmihci, N. :
Pathogenesis of progressive rod-cone degeneration in miniature poodles. Invest Ophthalmol Vis Sci 23:610-30, 1982. Pubmed reference: 6215376.

Edit History


  • Created by Frank Nicholas on 16 Oct 2006
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 02 Dec 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 27 Sep 2019
  • Changed by Frank Nicholas on 03 Oct 2019
  • Changed by Frank Nicholas on 03 Feb 2020
  • Changed by Imke Tammen2 on 19 Apr 2022
  • Changed by Imke Tammen2 on 21 Apr 2022
  • Changed by Imke Tammen2 on 22 Apr 2022
  • Changed by Imke Tammen2 on 12 Jan 2023
  • Changed by Imke Tammen2 on 18 Aug 2023
  • Changed by Imke Tammen2 on 01 Dec 2023