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Cerebellar degeneration and myositis (CDMC) - Nova Scotia duck tolling retriever

Neurological · Dog

Hereditary neurodegenerative disease of the Nova Scotia duck tolling retriever that combines cerebellar degeneration and inflammatory myositis. It appears between 10 weeks and 6 months of age as progressive ataxia with hypermetria and, in many cases, muscle weakness and episodes of collapse. Serum creatine kinase (CK) is markedly elevated (3-25 times the upper limit) and MRI shows bilateral lesions in the cerebellum and masticatory muscles. The prognosis is poor and affected dogs are usually euthanised.
Inheritance patternAutosomal recessive. Affected homozygotes; asymptomatic carrier heterozygotes.
Gene / MutationSLC25A12 XM_038584842.1:c.1337C>T (p.Pro446Leu), NSDTR-specific variant. The p.L349P variant of the same gene (Shelton 2019) is specific to the Dutch Shepherd and should not be used for the NSDTR.
PenetranceComplete penetrance is described in homozygotes; heterozygotes are asymptomatic carriers.
Codervyr
Turnaround time15 days
Price52,60 €

Incidence

Specific to the Nova Scotia duck tolling retriever. Estimated allele frequency of 3.6% in the European population and 1.3% in the North American one, with carrier frequencies of 7.1% and 2.7%, respectively. No cases have been described outside the breed.

Breeder management

- Test breeding animals before mating; prioritise lines with a neurological or muscular history\n- Do not cross two carriers: 25% risk of affected homozygotes\n- A carrier can be mated with a clear animal; offspring intended for breeding must be tested\n- Progressively replace carriers with clear offspring without narrowing the gene pool\n- In the face of a puppy with ataxia and elevated CK, confirm the genotype before planning matings of the parents

Specialist notes

The differential diagnosis must include immune-mediated inflammatory myopathies, muscular dystrophies and other cerebellar ataxias of the NSDTR. Elevated CK and MRI with bilateral lesions in the cerebellum and masticatory muscles point towards CDMC. Muscle biopsy shows invasive lymphohistiocytic fibre myositis without evidence of an infectious agent. Do not confuse with the p.L349P variant (Dutch Shepherd).

References

1. Christen M et al. 2022, SLC25A12 missense variant in Nova Scotia Duck Tolling Retrievers affected by cerebellar degeneration-myositis complex (CDMC). Genes (Basel) 13(7):1223. PMID: 35886006. 2. Shelton GD et al. 2019, A mutation in the mitochondrial aspartate/glutamate carrier leads to a more oxidizing intramitochondrial environment and an inflammatory myopathy in Dutch Shepherd dogs. J Neuromuscul Dis 6(4):485-501. PMID: 31594244 (variante p.L349P, Pastor holandés). OMIA:002294-9615.

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