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Inherited Myopathy Great Dane Type (CNM)
| Acronym: | CNM, IMGD |
| Gene: | BIN1 |
| Mutation: | c.786-2A>G |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Inherited myopathy Great Dane type (CNM) is a hereditary, non-inflammatory myopathy affecting young Great Danes. It is a degenerative muscle disorder with an early age of onset. The first form of myopathy in dogs was registered in the 1970s and the affected dog was a Labrador retriever breed. The form of myopathy detected in Laboratory retrievers differs from myopathy in Great Danes and it is caused by a different mutation. Inherited myopathy in Great Danes was originally reported in 1994. as a central core myopathy, the same as central core myopathy condition in humans. Inherited myopathy in Great Danes can be histologically confirmed with the characteristic centrally located cytoarchitectural abnormalities. A myopathy with similar features has been described in male springer spaniel, sheep, and cattle. The first symptoms of the inherited myopathy Great Dane type usually occur before one year of age and it is identified in both sexes. The disorder is characterized by progressive exercise intolerance, muscle wasting, and an exercise-induced tremor. After exercise, affected dogs collapse into sternal recumbent. The time duration of the exercise before the dog’s collapse varies and depends on the severity of the disorder. In severely affected dogs, it is needed only a few steps to induce the collapse and in mildly affected dogs, up to 60 minutes of exercise are possible. The condition frequently found in affected dogs has elevated serum creatinine kinase concentrations and spontaneous electrical activity in skeletal muscles. Research revealed generalized muscle atrophy when affected dogs were compared with unaffected siblings. A tremor in affected dogs is present also when standing and becomes more prominent with movement and excitement.
Inherited myopathy in Great Danes is caused by a mutation in the BIN1 gene. The disorder is inherited in an autosomal recessive manner. In case of showing the CNM symptoms, the healthy parents of the affected cub are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. There is no cure for this disorder, and the only way to prevent it is to breed dogs that are not carriers of the mutation. Defected genes for autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. The only way to find out if there is a chance of getting an affected puppy is to do genetic testing.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Böhm J, Vasli N, Maurer M, Cowling BS, Shelton GD, Kress W, Toussaint A, Prokic I, Schara U, Anderson TJ, Weis J, Tiret L, Laporte J. Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy. PLoS Genet. 2013 Jun;9(6).
Lujan Feliu-Pascual, A. (2006): Inherited myopathy of great Danes. Journal of Small Animal Practice (2006) 47,249–254.