OMIA 001554-9615 : Multifocal retinopathy 3 in Canis lupus familiaris
Category: Vision / eye phene
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: 2010
Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)
Species-specific name: cmr3
Species-specific description: Canine multifocal retinopathy (cmr) is an ocular disorder characterized by multiple areas of retinal degeneration. The disorder detailed in this entry (cmr3) has essentially the same cinical signs as the other two forms of cmr (namely cmr1 [OMIA001553-9615] and cmr2 [OMIA001554-9615]), but as explained by Zangerl et al. (2010), the nature of the cmr3 mutation, which has been seen in only one breed (Lapponian Herder), suggests a different molecular mechanism.
Molecular basis: The causative mutations for Cmr3 in the Lapponian herder are a deletion and a G to T substitution in exon 10 of BEST1 (Zangerl et al., 2010).
Clinical features: Signs of cmr 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, progressing as the dog 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.
Breed: Lapponian Herder .
|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|
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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|
|737||Lapponian Herder||Multifocal retinopathy 3||BEST1||cmr3||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||18||g.54470590del||c.1388del||p.(P463Hfs)||NM_001097545.1; NP_001091014.1; published as c.1388delC||rs397509969||2010||21197113||Variant information and allele abbreviation gleaned from or confirmed by Donner et al. (2016) PLoS One 11:e0161005 and genomic position in CanFam3.1 and EVA ID provided by Mateo Etcheveste and Robert Kuhn.|
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.
|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.|
|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.|
|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.|
|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.|
|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.|
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