CMR2 - Canine multifocal retinopathy type 2

Canine multifocal retinopathy (CMR) is a hereditary disease. Most often affected dog breeds are: Great Pyrenees, English Mastiffs, Bullmastiffs, Coton de Tulear and related breeds.

CMR symptoms are very similar to Best macular dystrophy disease (BMD) in humans. BMD and CMR are retinal disorders caused by mutation in VMD2 gene (Vitelliform Macular Dystrophy 2 Gene). VMD2 gene is coding a protein bestrophin which is responsible for right forming of pigment epithelium in retina. Mutations in VMAD2 gene cause pigment epithelium athrophy which is leading to serious damage of sight.

Two VMD2 gene mutations responsible for CMR in dogs were identified:

• Mutation C73T in exon 2 causing CMR1 in Great Pyrenees, English Mastiffs, Bullmastiffs and related breeds. This mutation causes forming of premature stop codon in positi on 25 ( R25X) of VMD2 gene.
• Mutation G482A in exon 5 causing CMR2 in Coton de Tulear. That leads to glycine to aspartic acid change in position 161 of protein sequence (G161D).

CMR disease usually arises before 4th month of age in an affected puppy. Clinically, rose-grey coloured lesions are remarkable in retina. These lesions are of different size and shape and are occured in both eyes of affected individual. Total blindness usually comes in higher age.

CMR is an autosomal recessive disorder. The disease affects dogs with P/P (positive / positive) genotype only. Dogs with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

References:
Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, and Gustavo D. Aguirre
Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model for Best Disease. Invest. Ophthalmol. Vis. Sci., May 2007; 48: 1959 - 1967.