Polyneuropathy 2 (LPN2)

 

Gene: GJA9

Transmission: Autosomal Dominant (variable expression; i.e. complexe inheritance)

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Deletion, GJA9 gene; c.1107_1108 del.AG, p.(A370N fs STOP 12), exon1

Medical system: Neurologic

Breeds: Dachshund Miniature Longhair/Shorthair, Leonberger

Age of onset of symptoms: 6 years on average (quite variable, from 1 to 10 years)

Polyneuropathy is a general term for a family of hereditary diseases of nerves and nerve cells that can affect dogs.  These diseases can involve a number of mutations in a number of genes, some that are known and many that are not as yet characterized.  The LPN2 disease is a hereditary polyneuropathy seen in the Leonberger breed of dogs.  Clinical signs are similar to what is seen for LPN1 disease, including weakness, hypotonia, muscle atrophy due to denervation, breathing difficulty (dyspnea) and laryngeal paralysis.  The age of onset of clinical signs is variable but on average 6 years, which is later than for LPN1.  The heredity of LPN2 is said to be dominant with variable penetration.  Since disease signs occur after the age of reproduction, it is important to perform DNA testing and selective breeding in order not to produce the M/N and M/M mutant animals that will be at risk of the disease.

 

References:

OMIA link: [2119-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Becker D, Minor KM, Letko A, et al. (2017) A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs.  BMC Genomics 18:662. [pubmed/28841859]

Granger N. (2011) Canine inherited motor and sensory neuropathies: an updated classification in 22 breeds and comparison to Charcot-Marie-Tooth disease. Vet J 188:274-85.  [pubmed/20638305]

Shelton GD, Podell M, Poncelet L, et al. (2003) Inherited polyneuropathy in Leonberger dogs: a mixed or intermediate form of Charcot-Marie-Tooth disease? Muscle Nerve. 27(4):471-7. [pubmed/12661049]