Genetic basis of CMR3 - is an inherited eye disease caused by mutations in the BEST1 gene (Bestrophin 1). The specific mutations associated with CMR3 include a deletion (c.1388delC) and a substitution (c.1466G>T) in exon 10 of the BEST1 gene. These mutations result in incomplete or dysfunctional bestrophin protein, which is crucial for normal retinal pigment epithelium (RPE) function. The disease is inherited in an autosomal recessive manner; dogs must inherit two copies of the mutated gene to be affected, while carriers with one copy do not show symptoms but can pass the mutation on.

Pathophysiology - CMR3 affects the retina by causing multiple, discrete circular areas of retinal detachment typically occurring between 9 and 24 months of age. Fluid accumulates underneath the detached retina, forming gray, tan, orange, or pink "blisters" visible on the retina. Retinal pigment epithelium shows vacuolation, hypertrophy, and separation from underlying membrane in affected areas. Progression of retinal changes is usually slow and often does not lead to blindness, although some vision loss has been reported. In some dogs, the blisters may diminish or appear to heal with age.

Clinical Signs and Breeds - Clinical signs include multiple tan-pink subretinal lesions observed in both tapetal and non-tapetal areas of the fundus. The Finnish Lapphund, Lapponian Herder, and Swedish Lapphund are the primary breeds known to carry the CMR3 mutations and exhibit the disease. Vision deficits are uncommon but can occur in some affected dogs.

Why This Matters to Breeders and Vets - Genetic testing is available to identify carriers and affected dogs to prevent breeding affected puppies. Dogs with genotype: N/N (normal) are clear and cannot transmit CMR3. N/CMR3 (carriers) do not have disease but can pass the mutation to offspring. CMR3/CMR3 (affected) will develop the disease and transmit it to all offspring. Breeders should avoid mating two carriers to prevent producing affected puppies, which represents a 25% risk per litter. Understanding CMR3 supports better eye health management and breeding decisions in the affected breeds.

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