Canine degenerative myelopathy (DM) is a late-onset, progressive, neurodegenerative disorder with a fatal outcome, occurring in a vast number of dog breeds. Most dogs are at least eight years of age when they begin to show clinical signs, starting with general proprioceptive ataxia in the hind limbs and upper motor neuron paraparesis, evolving to lower motor neuron tetraplegia and brain stem signs. A definitive diagnosis can only be made postmortem by the histopathological observation of neuronal degradation and demyelination of the spinal cord. Most DM-affected dogs are homozygous for one of the known superoxide dismutase 1 gene (SOD1) mutations (ENSCAFT00000065394.1:c.82G>A, first described as NM_001003035.1:c.118G>A). A second mutation (NM_001003035.1:c.52A>T) in the same gene has been found but occurs only in Bernese mountain dogs. Not every homozygous dog develops the disease; this indicates that the disease is incompletely penetrant and that modifier loci might be present. In this review, the authors aim to give an overview of the disease progression and the current genetic knowledge of DM, which is of paramount importance for the correct diagnosis and to help reduce the disease incidence.
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