OMIA:001444-9615 : Multifocal retinopathy 1 in Canis lupus familiaris |
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 153700 (trait) , 611809 (trait) , 193220 (trait) , 613194 (trait) , 607854 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2007
Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)
Species-specific name: Canine multifocal retinopathy
Species-specific symbol: cmr1
Species-specific description: Canine multifocal retinopathy (cmr) is an ocular disorder characterized by multiple areas of retinal degeneration. The detection of three different mutations in the one gene (BEST1) has led to the naming of three different forms of the disorder (cmr1 [OMIA001444-9615], cmr2 [OMIA001553-9615], cmr3 [OMIA001554-9615]), all of which are very similar clinically, but with the last two each occurring in only one breed. The form of cmr detailed in this entry (cmr1) occurs in several breeds (listed below).
Mapping: CFA18
Molecular basis: The causative mutation of cmr1 in the Great Pyrenees, the English mastiff and the bullmastiff is a C to T mutation that generates a premature stop codon: c.73C>T; p.Arg25Ter (Guziewicz et al., 2007).
Gornik et al. (2014) reported this same causal mutation in a Boerboel.
Clinical features: Signs of cmr1 develop around 13 weeks of age, and include multiple tan-pink subretinal patches in both the tapetal and the non-tapetal fundus along with focal areas of tapetal hyper-reflectivity. The lesions elevate the retina. They progress as the animal ages to focal areas of retinal degeneration and retinal pigment epithelial hypertrophy and pigmentation (Grahn et al., 1998).
Pathology: In retinal histology there are multiple areas of retinal pigment epithelial vacuolation, hypertrophy, apparent separation from Bruch’s membrane, and multiple serous retinal detachments (Grahn et al., 1998).
Control: Relatives of affected dogs should be tested. Breeding of affected or carrier animals is not recommended. If carriers must be bred, it should be bred only to a tested, homozygous normal dog.
Genetic testing: There are tests available to detect the known causative mutations.
Breeds: American Bulldog, Australian Shepherd, Boerboel, Bull Mastiff, Dogue de Bordeaux, English Bulldog, English Mastiff, Great Pyrenees, Italian Cane Corso, Perro de Presa Canario.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| BEST1 | bestrophin 1 | Canis lupus familiaris | 18 | NC_051822.1 (55534952..55522441) | BEST1 | Homologene, Ensembl , NCBI gene |
Variants
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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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 275 | Boerboel Bull Mastiff English Mastiff Great Pyrenees | Multifocal retinopathy 1 | BEST1 | cmr1 | nonsense (stop-gain) | Naturally occurring variant | CanFam3.1 | 18 | g.54478586G>A | c.73C>T | p.(R25*) | NM_001097545.1; NP_001091014.1 | 2007 | 17460247 | Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool |
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 | 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. | |
| 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. | |
| Gornik, K.R., Pirie, C.G., Duker, J.S., Boudrieau, R.J. : | |
| Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel. Vet Ophthalmol 17:368-72, 2014. Pubmed reference: 23998685 . DOI: 10.1111/vop.12095. | |
| 2013 | Guziewicz, K.E., Zangerl, B., Komáromy, A.M., Iwabe, S., Chiodo, V.A., Boye, S.L., Hauswirth, W.W., Beltran, W.A., Aguirre, G.D. : |
| Recombinant AAV-Mediated BEST1 Transfer to the Retinal Pigment Epithelium: Analysis of Serotype-Dependent Retinal Effects. PLoS One 8:e75666, 2013. Pubmed reference: 24143172 . DOI: 10.1371/journal.pone.0075666. | |
| 2012 | Guziewicz, K.E., Aguirre, G.D., Zangerl, B. : |
| Modeling the Structural Consequences of BEST1 Missense Mutations. Adv Exp Med Biol 723:611-8, 2012. Pubmed reference: 22183385 . DOI: 10.1007/978-1-4614-0631-0_78. | |
| Hoffmann, I., Guziewicz, K.E., Zangerl, B., Aguirre, G.D., Mardin, C.Y. : | |
| Canine multifocal retinopathy in the Australian Shepherd: a case report. Vet Ophthalmol 15 Suppl 2:134-8, 2012. Pubmed reference: 22432598 . DOI: 10.1111/j.1463-5224.2012.01005.x. | |
| 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 | Guziewicz, KE., Slavik, J., Lindauer, SJ., Aguirre, GD., Zangerl, B. : |
| Molecular Consequences of BEST1 Gene Mutations in Canine Multifocal Retinopathy Predict Functional Implications for Human Bestrophinopathies. Invest Ophthalmol Vis Sci 52:4497-505, 2011. Pubmed reference: 21498618 . DOI: 10.1167/iovs.10-6385. | |
| 2010 | Zangerl, B., Wickström, K., Slavik, J., Lindauer, S.J., Ahonen, S., Schelling, C., Lohi, H., Guziewicz, K.E., Aguirre, G.D. : |
| Assessment of canine BEST1 variations identifies new mutations and establishes an independent bestrophinopathy model (cmr3). Mol Vis 16:2791-804, 2010. Pubmed reference: 21197113 . | |
| 2007 | Guziewicz, KE., Zangerl, B., Lindauer, SJ., Mullins, RF., Sandmeyer, LS., Grahn, BH., Stone, EM., Acland, GM., Aguirre, GD. : |
| Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease. Invest Ophthalmol Vis Sci 48:1959-67, 2007. Pubmed reference: 17460247 . DOI: 10.1167/iovs.06-1374. | |
| 1998 | Grahn, BH., Philibert, H., Cullen, CL., Houston, DM., Semple, HA., Schmutz, SM. : |
| Multifocal retinopathy of Great Pyrenees dogs. Vet Ophthalmol 1:211-221, 1998. Pubmed reference: 11397233 . |
Edit History
- Created by Frank Nicholas on 04 Mar 2011
- Changed by Vicki Meyers-Wallen on 28 Sep 2011
- Changed by Frank Nicholas on 29 Sep 2011
- Changed by Frank Nicholas on 08 Dec 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 15 May 2015
- Changed by Imke Tammen2 on 22 Aug 2021