OMIA 001553-9615 : Multifocal retinopathy 2 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: cmr2

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 (cmr2) occurs only in the Coton du Tulear breed.

Mapping: CFA18

Molecular basis: The causative mutation for cmr2 in the Coton de Tulear is a G to A missense mutation in BEST1 (Guziewicz et al., 2007).

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: Coton de Tulear.

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. 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.

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
Coton de Tulear Multifocal retinopathy 2 BEST1 cmr2 missense c.482G>A p.G161D 2007 17460247

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.
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.
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.
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 12 Dec 2011