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Degenerative Myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord that typically develops later in life and gradually causes loss of hind-limb coordination and mobility.
For most dog breeds, genetic testing for DM focuses on the well-known SOD1 c.118G>A variant located in exon 2. Bernese Mountain Dogs are different.
In this breed, a second DM-associated SOD1 variant has been identified: SOD1 c.52A>T in exon 1. This variant has so far been reported specifically in the Bernese Mountain Dog and represents an additional genetic risk that is not detected by the conventional DM exon 2 test.
This means that a Bernese Mountain Dog that tests clear for the common DM exon 2 variant is not necessarily genetically clear for SOD1-associated degenerative myelopathy.
For a complete genetic assessment of DM risk in the Bernese Mountain Dog, both DM Exon 1 and DM Exon 2 should therefore be considered. This is also the recommendation of the Bernese Mountain Dog Club of America.
The affected gene is SOD1 – Superoxide Dismutase 1.
SOD1 encodes an intracellular antioxidant enzyme involved in protecting cells against oxidative damage caused by reactive oxygen species.
Mutations affecting SOD1 are particularly important in neurodegenerative disease because altered SOD1 protein can become structurally unstable and form abnormal protein aggregates within neurons.
Similar SOD1-associated mechanisms are known in some forms of human amyotrophic lateral sclerosis (ALS), which is one reason canine degenerative myelopathy has been extensively investigated as a comparative model of neurodegeneration.
In the original Bernese Mountain Dog affected by DM Exon 1, abnormal SOD1-positive protein aggregates were demonstrated within spinal cord motor neurons, resembling those observed in dogs affected by DM associated with the more common exon 2 mutation.
The Bernese Mountain Dog-specific DM variant is:
SOD1 c.52A>T
located in exon 1 of the SOD1 gene.
The original 2011 study described the resulting amino-acid substitution as:
p.Thr18Ser (p.T18S)
meaning that threonine at amino-acid position 18 is replaced by serine.
The variant was discovered in a Bernese Mountain Dog with clinically and histopathologically confirmed degenerative myelopathy that was homozygous normal for the conventional SOD1 c.118G>A exon 2 mutation.
Sequencing of all five SOD1 exons identified homozygosity for the previously unrecognised c.52A>T variant.
Subsequent population studies found the SOD1 c.52T allele only in Bernese Mountain Dogs, while the common c.118A DM allele occurs across many breeds.
The DM Exon 1 variant appears to be considerably less common than the conventional Exon 2 DM variant.
In a large study involving 912 Bernese Mountain Dogs, 59 were heterozygous and two were homozygous for the SOD1 c.52T allele, corresponding to an estimated allele frequency of approximately 3.5% in that dataset.
A more recent Italian dataset reported an allele frequency of approximately 7.6% for the c.52A>T variant among tested Bernese Mountain Dogs.
These figures should not be interpreted as exact worldwide breed frequencies because tested populations can differ geographically and may be affected by selection bias.
Nevertheless, they demonstrate that the mutation is present at a meaningful frequency in the breed.
Degenerative myelopathy associated with SOD1 variants is generally considered an autosomal recessive condition with incomplete penetrance.
For DM Exon 1 alone, typical laboratory results can be interpreted as:
However, Bernese Mountain Dogs require a more sophisticated interpretation because two separate DM-associated mutations exist in SOD1.
The two important SOD1 variants are:
DM Exon 1:
SOD1 c.52A>T
DM Exon 2:
SOD1 c.118G>A
A Bernese Mountain Dog can therefore carry a mutation at one SOD1 locus while appearing clear or only carrier at the other.
This creates the possibility of compound heterozygosity.
For example:
Exon 1: N/DM1
Exon 2: N/DM2
Such a dog can carry one different pathogenic SOD1 variant on each chromosome.
This is biologically important. In the large breed-distribution study, 24 Bernese Mountain Dogs were heterozygous at both SOD1 loci and were considered likely compound heterozygotes. Among six older double-heterozygous dogs for which clinical information was available, four developed signs compatible with DM, including one dog with histopathologically confirmed disease.
The Bernese Mountain Dog Club of America therefore considers dogs with two copies of either mutation, or one copy of each mutation, to be genetically at risk and recommends testing for both.
This is the major reason why testing only the common DM Exon 2 mutation is incomplete in this breed.
DM is generally a late-onset, progressive neurological disease.
The original Bernese Mountain Dog with the Exon 1 mutation developed a slowly progressive neurological syndrome consistent with classical canine degenerative myelopathy.
Early clinical signs can include:
A characteristic feature is that significant spinal pain is usually absent.
As disease progresses, affected dogs can develop:
DM progression is variable. The original Bernese Mountain Dog Exon 1 case progressed over approximately 21 months, somewhat more slowly than some classical descriptions of DM.
The DNA test answers a specific question:
Does this Bernese Mountain Dog carry the SOD1 c.52A>T Exon 1 variant?
It does not prove that neurological signs in an individual dog are caused by degenerative myelopathy.
This distinction is essential.
A Bernese Mountain Dog with hind-limb weakness may have other conditions including:
Clinical diagnosis of DM therefore requires neurological assessment and exclusion of other plausible causes.
Depending on the patient, this can include laboratory testing, neurological examination and advanced spinal imaging such as MRI.
Even today, definitive diagnosis of DM remains histopathological, whereas diagnosis during life is generally presumptive and based on compatible clinical progression, SOD1 genotype and exclusion of competing diagnoses.
There is currently no established curative therapy that reverses the underlying neurodegeneration of canine DM.
Treatment is therefore focused on maintaining mobility, independence and quality of life for as long as possible.
Management commonly includes:
A 2023 survey of veterinary neurologists and rehabilitation professionals found that exercise and physical rehabilitation were among the most commonly recommended management strategies for dogs with DM.
Earlier retrospective work also found substantially longer survival in dogs receiving intensive controlled physiotherapy compared with dogs receiving moderate or no physiotherapy.
No supplement or medication should currently be presented as a proven cure for DM.
For the Exon 1 mutation considered alone:
N/N × N/N
→ all puppies expected to be clear for the tested Exon 1 variant.
N/N × N/DM1
→ approximately 50% clear and 50% carriers.
N/DM1 × N/DM1
→ approximately 25% clear, 50% carriers and 25% homozygous DM1/DM1.
DM1/DM1 × N/N
→ all puppies expected to inherit one Exon 1 variant.
However, Bernese Mountain Dog breeding decisions should not be made from the Exon 1 result alone.
The intended mating partner should also be evaluated for DM Exon 2, because one Exon 1 mutation together with one Exon 2 mutation can create a potentially at-risk compound heterozygous offspring.
For example:
Parent 1: carrier DM Exon 1
Parent 2: carrier DM Exon 2
can produce puppies that inherit:
one Exon 1 mutation + one Exon 2 mutation
and therefore carry two different SOD1 DM-associated alleles.
This is why reporting the two tests independently while interpreting them together is particularly important in Bernese Mountain Dogs.
No.
A conventional DM result normally refers to:
SOD1 c.118G>A – Exon 2
A Bernese Mountain Dog can test clear for this variant while carrying:
SOD1 c.52A>T – Exon 1.
This exact situation led to the discovery of the Bernese-specific mutation: the original affected dog had degenerative myelopathy despite being homozygous wild type at the conventional c.118 locus.
Therefore, for Bernese Mountain Dogs:
DM Exon 1 + DM Exon 2 provides a substantially more complete genetic assessment than either test alone.
Current evidence indicates that the SOD1 c.52A>T Exon 1 variant is specifically associated with the Bernese Mountain Dog.
In the large breed-distribution study, more than 1,600 dogs were tested for this locus. The c.52T variant was identified in Bernese Mountain Dogs but not in the other tested breeds or mixed-breed dogs.
For this reason, DM Exon 1 should be regarded as a Bernese Mountain Dog-specific genetic test, whereas the common DM Exon 2 variant occurs across many breeds.
Bernese Mountain Dogs represent an unusual and important example where the same inherited neurological disease can be associated with two different pathogenic variants within the same gene.
Testing both variants can identify:
Testing only one mutation can therefore give an incomplete picture of DM-associated genetic risk in this breed.
The Bernese Mountain Dog Club of America specifically recommends testing for both DM mutations.
Both are variants in the SOD1 gene, but they occur at different positions.
DM Exon 1 is SOD1 c.52A>T and is associated specifically with Bernese Mountain Dogs.
DM Exon 2 is SOD1 c.118G>A and is the common DM-associated variant found across many dog breeds.
Yes.
Testing only Exon 2 can miss the Bernese-specific Exon 1 mutation. Testing only Exon 1 can miss the considerably more widespread Exon 2 mutation.
Yes.
A Bernese Mountain Dog can carry one copy of the Exon 1 variant and one copy of the Exon 2 variant.
Such dogs are important because evidence indicates that compound heterozygotes can be at increased risk for clinical DM.
No.
SOD1-associated DM shows incomplete penetrance. A genetically at-risk dog may never develop clinical disease during its lifetime.
Genotype therefore indicates genetic risk, not certainty of future neurological disease.
No.
DNA testing establishes genetic status. A dog with neurological symptoms requires veterinary clinical evaluation because many other spinal and neurological disorders can resemble DM.
There is currently no established curative treatment. Management focuses primarily on rehabilitation, maintaining mobility and supporting quality of life.
Veterinary genetics disclaimer:
A DNA result applies to the specific genetic variant tested. DM-associated SOD1 variants indicate genetic status and susceptibility but do not by themselves establish a clinical diagnosis of degenerative myelopathy.
In Bernese Mountain Dogs, both SOD1 c.52A>T (Exon 1) and SOD1 c.118G>A (Exon 2) should be considered when interpreting genetic risk and planning breeding combinations.
Genetic testing does not replace neurological examination or other appropriate veterinary diagnostics.