Degenerative myelopathy risk modifier (DMRM)

LABOKLIN Service ID: 8939

Canine degenerative myelopathy (DM) is a severe, slowly progressing neuro degenerative disease with a late onset (age 8 years or older). The disease is characterised by degeneration of axons and myelin in the chest and lumbar parts of the spinal cord. The initial clinical sign is characterized by spastic and general proprioceptive ataxia of the hind limbs. Hyporeflexia of the myotactic and withdrawal reflexes occur. As the disease progresses, the frequently observed asymmetric weakness ascends to affect the thoracic limbs, so that affected dogs lose the ability to walk 6 months to 2 years after the onset of symptoms. Late in progression of the disease, fecal and urinary incontinence can be observed. In affected small breeds, the disease often progresses more slowly than in affected large dog breeds.
Because of the similarity of the symptoms, the differentiation between DM and other neuromuscular or skeletal diseases can be very difficult. A definitive diagnosis can only be made postmortem by the histopathological observation of neuronal degradation and demyelination of the spinal cord. However, a genetic variant in exon 2 of SOD1 (superoxide dismutase 1) gene was identified as major risk factor for developing DM in many breeds so far. Since not every dog homozygous for the SOD1 variant develops the disease (incomplete penetrance) and since there is a variable presentation between breeds, it is assumed that other genetic and/or environmental factors play a role in development and expression of DM.
In the breed Pembroke Welsh Corgi (PWC), a risk haplotype (also called risk modifier) within the SP110 nuclear body protein gene has been found to increase the risk of SOD1 homozygous affected dogs to develop DM. While some SOD1 affected dogs of this breed develop symptoms at a relatively early age (7-9 years), others reached 15 years of age without any signs of DM. The risk modifier has been more often identified in dogs with an early onset of the disease than in dogs that do not show any symptoms even at older ages. Therefore, the risk modifier affects the overall risk to develop symptoms of the disease as well as the age of onset in SOD1 affected dogs of the PWC breed. Since one copy of the risk haplotype is sufficient to increase the risk, the variant seems to have a dominant effect.
The risk haplotype has also been detected in other breeds, but it is still unknown if this variant has an effect on the risk of developing DM in SOD1 affected dogs in breeds other than the PWC breed.
Please note that testing for the SP110 risk modifier is only needed for dogs that are homozygous affected for the SOD1 risk factor.

Method	sequencing
Breed list	Pembroke Welsh Corgi
Heredity	autosomal dominant
Duration	1 - 2 weeks after arrival of the sample