Polioencephalopathy (PE) Eurasier
Polioencephalopathy is characterized by initial onset of movement disorder episodes and progressive impairment of motor function, but preserved consciousness and behavior. For an inborn form of PE in Eurasier dogs a potential causative genetic variant has been discovered in the MECR gene in a small UK-based family. In this family the variant is consistent with an autosomal recessive mode of inheritance. Current studies are focused on determining the prevalence of this genetic variant in unrelated lineages and evaluating its broader contribution to the genetic etiology of Polioencephalopathy within the breed.
General Information
In Polioencephalopathy (PE), the grey matter of the brain, where the nerve cells are located, is damaged. Neurological deficits of all kinds are the result; their diversity does not allow any conclusions to be drawn about the cause. They are usually triggered by exogenous metabolic disorders, e.g. due to poisoning or malnutrition. In humans, congenital defects in the mitochondria have been described as the main genetic causes.
In a recent study, three littermates of Eurasier puppies were diagnosed with PE in which initial episodes of movement disorders and progressive impairment of motor function were observed; consciousness and behaviour remained unchanged. Genome analysis of one of the affected animals led to a variant (c.823A>G) in the MECR gene as a possible cause of this presumably hereditary and progressive PE. Both parents were heterozygous (N/mecr) for the variant; 115 Eurasier control dogs outside the UK were free (N/N). The similarity to a rare form of childhood dystonia reported in humans with MECR loss-of-function variants is striking.
In addition, a further homozygous missense variant in the ATG4D gene was identified in 2 of the 3 puppies in the litter. The study suggests that the ATG4D missense mutation may be additive in these dogs and may lead to a more severe clinical phenotype.
Investigations into the occurrence of the variant in Eurasier populations should help to clarify the relationship between MECR variants and the occurrence of rare PE in the Eurasier population.
Symptoms
Eurasier dogs affected by inborn PE show early onset movement disorders that worsen as the disease progresses. Typical symptoms are
- persistent divergent strabismus
- episodes of generalised ataxia
- wide-spreading gait with the front legs and their uncontrolled bending and stretching movements.
Consciousness and behaviour remain intact in all dogs.
Affected breeds
Dogs of the Eurasier breed and mixed breeds in which Eurasiers are involved.
As long as the origin of the mutation hasn’t been clarified, the breeds from which the Eurasier breed was formed (Samoyed, Chow-Chow, Wolfspitz) are also potentially segregating the mutation.
Test information
The test is based on a PCR-based amplification of the DNA section in which the mutation is located. It involves the exchange of a single base pair (c.823A>G), which can be recognized by sequencing the PCR product or other diagnostic methods.
Please order at: Polioencephalopathy (PE) Eurasier
Overview of potential test results
Result: N/N
Short statement: homozygous normal - healthy
Explanation: The tested animal does not have the mutation in any allele of the MECR gene and therefore cannot pass it on to offspring. When mated with a heterozygous carrier, 50% of the offspring are heterozygous, 50% are homozygous wildtype.
Result: N/mecr
Short statement: heterozygous - healthy
Explanation: The animal carries the mutant allele in one of the two copies of the MECR gene and will transmit it to 50% of its offspring. The tested animal will not show symptoms related to the variant; it is not advisable to exclude carriers from breeding as long as the pathogenicity of the MECR variant is under investigation. However, to prevent homozygous affected offspring mating should be carried out with MECR N/N-tested animals only.
Result: mecr/mecr
Short statement: homozygous for the mutation - affected
Explanation: The animal has the analysed variant in both alleles of the MECR gene. Homozgous mutant dogs are expected to show the clinical symptoms of Polioencephalopathy. However, since the MECR variant pathogenicity is still under investigation it is not possible to provide a final statement for breeding and veterinary management.
So far, this result has only been observed in the puppies on which the study has been based.
Literature
- Rawson F, Christen M, Rose J, Paran E, Leeb T, Fadda A. Polioencephalopathy in Eurasier dogs. J Vet Intern Med. 2024 Jan-Feb;38(1):277-284. doi: 10.1111/jvim.16945. Epub 2023 Dec 2. PMID: 38041431; PMCID: PMC10800227.
https://onlinelibrary.wiley.com/share/6TDKDJJVIRKPXERQXBDC?target=10.1111/jvim.16945
- Online Mendelian Inheritance in Animals