Polyneuropathy (LPN1), juvenile

 

Gene: ARHGEF10

Transmission: Autosomal recessive (most likely)

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, ARHGEF10 gene; c.1955+6 del10bp, exon17+intron17-18

Medical system: Neurological

Breeds: Leonberger, Saint-Bernard

Age of onset of symptoms: 2 years on average

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.  LPN1 in the St-Bernard and the Leonberger is a hereditary polyneuropathy that is characterized by progressive neuromuscular degeneration.  Affected animals begin to show signs of weakness, muscle atrophy and motion incoordination by the age of 2 years on average.  This condition progresses to the point that affected animals cannot support the weight of their hind legs.  In addition, they lose their ability to bark and suffer from respiratory problems such as laryngeal paralysis.  Affected animals are usually euthanized in the terminal phase of the disease.  It should be noted that the characterized mutation in the ARHGEF10 gene accounts for only 20% of neuropathies seen in Leonbergers.

 

References:

OMIA link: [1917-9615]

Ekenstedt KJ, Becker D, Minor KM, Shelton GD, et al. (2014) An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs. PLOS Genetics 10(10), e1004635. [pubmed/25275565]

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]