Polyneuropathy (Leonberger Type 2)

Other Names: Leonberger Polyneuropathy 2, LPN2, PN
Affected Genes: GJA9
Inheritance: Autosomal Dominant With Incomplete Penetrance
Mutation: chr15:3863524-3863525: 2bp deletion (AG)

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Common Symptoms

Polyneuropathy (Leonberger type 2) is an inherited neurologic disease affecting Leonbergers. Affected dogs exhibit clinical signs of generalized neurologic disease including weakness, loss of muscle tone, muscle Atrophy, awkward high-stepping gait in the hind limbs, decreased reflexes, abnormal bark sounds and increased breathing sounds due to paralysis of the larynx. The average age of onset for affected dogs is six years of age, though the age of onset is variable and can range from 1-10 years of age. With time, the disease may progress to the point that affected dogs are unable to bear weight or walk.


Breed-Specific Information for the Leonberger

The Mutation of the GJA9 gene associated with polyneuropathy (Leonberger type 2) has been identified in Leonbergers. Though the exact frequency in the overall Leonberger population is unknown, of the 7,455 Leonbergers tested in one study, 6% had one copy of the mutation and 0.2% had two copies with an overall frequency of at risk dogs of 6.2%.


Testing Tips

Genetic testing of the GJA9 gene in Leonbergers will reliably determine whether a dog is a genetic Carrier of polyneuropathy (Leonberger type 2). Polyneuropathy (Leonberger type 2) is inherited in an Autosomal Dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at-risk for the disease. Each pup that is born to a parent carrying one copy of the Mutation has a 50% chance of inheriting one copy of the GJA9 gene mutation and being at-risk for the disease. If both parents are affected, the chance of having affected offspring increases to 75-100%. Because symptoms may not appear until adulthood and not all dogs with the mutation develop disease, genetic testing should be performed before breeding. Reliable genetic testing is important for determining breeding practices. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers is not recommended. Leonbergers that are not carriers of the mutation have no increased risk of having affected pups due to this mutation. However, because there are multiple types of polyneuropathy caused by mutations in other genes, a normal result in GJA9 does not exclude polyneuropathy in a pedigree.


There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.


References

  • Becker D, Minor KM, Letko A, Ekenstedt KJ, Jagannathan V, Leeb T, Shelton GD, Mickelson JR, Drögemüller C. A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs. BMC Genomics. 2017 Aug 25;18(1):662. [PubMed: 28841859]
  • Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, Bley T, Oevermann A, Bilzer T, Leeb T, Drögemüller C, Mickelson JR. An ARHGEF10 deletion in highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs. PLoS Genet. 2014 Oct 2;10(10):e1004635. [PubMed: 25275565]