OMIA 001444-9615 : Multifocal retinopathy 1 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 153700 , 611809 , 193220 , 613194 , 608161

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_006600.3 (54483565..54468844) BEST1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Boerboel Bull Mastiff English Mastiff Great Pyrenees Multifocal retinopathy 1 BEST1 cmr1 nonsense (stop-gain) CanFam3.1 18 g.54478586C>T c.73C>T p.R25* 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.
2014 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
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