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Polyneuropathy, Juvenile-Onset Inherited (LPN1)/ Laryngeal Paralysis
Breeds
Relevance Rating: There is some evidence or research available for these breeds
General
Disease Name
Polyneuropathy, Juvenile-Onset Inherited (LPN1)/ Laryngeal Paralysis
OMIA
1917
Gene Name
ARHGEF10
Mutation
c.1955_1958+6delCACGGTGAGC
Test Type
Genetic Disease/Disorder
Details
This genetic test is unusual in that there are two disease names, with clinical descriptions by breed type. Please refer to the breed/disease combination for breed-specific information for this test. For both disease names/clinical symptoms the dogs suffer from neuromuscular disease(s).
Details 2
"LPN1 is a polyneuropathy resulting from a 10 base pair deletion within the gene ARHGEF10; dogs homozygous (D/D) for the LPN1 mutation typically develop clinical signs of disease before they reach 3 years of age. At present, LPN1 D/D dogs represent ~11% of all diagnosed cases of Leonberger polyneuropathy; a further 24% of dogs in our research population with a phenotype consistent with or diagnosis of unexplained polyneuropathy have the LPN1-D/N genotype (compared to 12.5% of healthy control dogs). The average age that clinical signs are first noted in these LPN1-D/N dogs, if they develop at all, is 6 years. Due to other causes of neuropathy in Leonbergers, the exact mode of inheritance of the LPN1 form of neuropathy cannot yet be stated for certain." [From University of MN] We have also identified LPN1 homozygous affected Saint Bernards with a biopsy confirmed polyneuropathy and clinical signs consistent with the disease. The LPN1 test can also be used in the Saint Bernard breed to aid in the diagnosis of polyneuropathy and to identify carriers in the breeding population. "The test for LPN1 does not account for all confirmed or suspected cases of laryngeal paralysis and polyneuropathy in the Saint Bernard breed. Until additional DNA-based test(s) are developed, the only way to confirm a suspected diagnosis of laryngeal paralysis is via laryngoscopy and/or nerve conduction study; polyneuropathy is diagnosed via a nerve and muscle biopsy." [From University of MN]
Published
Ekenstedt, K.J., Becker, D., Minor, K.M., Shelton, G.D., Patterson, E.E., Bley, T., Oevermann, A., Bilzer, T., Leeb, T., Drögemüller, C., Mickelson, J.R. : An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs. PLoS Genet 10:e1004635, 2014. Pubmed reference: 25275565. DOI: 10.1371/journal.pgen.1004635.
Published 2
An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, Bley T, et al. (2014) PLoS Genet 10(10): e1004635. doi:10.1371/journal.pgen.1004635
Published 4
A novel leukoencephalomyelopathy of Leonberger dogs. Oevermann, A., Bley, T., Konar, M., Lang, J. and Vandevelde, M. (2008), Journal of Veterinary Internal Medicine, 22: 467?471. doi:10.1111/j.1939-1676.2008.0068.x
Body/System/Process
Neurologic
OMIA Url
Inheritance
AR; RV
Breed Specific Info
Researched Breeds
Leonberger; Saint Bernard
Breed-specific 1
Leonberger
Breed-specific 1 Details
"Leonberger dogs may suffer from neuromuscular disease collectively termed Leonberger Polyneuropathy (LPN). LPN affected dogs may suffers from slowly worsening exercise intolerance and develop gait abnormalities, such as an exaggerated hitched step, especially in the hind limbs. There is often wasting of the hind limb muscles as well. Additionally, these dogs may have noisy breathing, a change in their bark, or even difficulty breathing due to involvement of the larynx and laryngeal folds in the throat. Eventually the disease may progress to the point where the dog cannot support its own weight and surgical intervention for laryngeal paralysis may be required. Biopsies of nerve from affected dogs show degradation of the nerve fibers and loss of myelin, the insulating material that normally helps speed messages along nerves. Muscle biopsies show atrophy resulting from nerve loss. Research carried out at the University of Minnesota, the University of Bern, and the University of California, San Diego - Comparative Neuromuscular Laboratory indicates that polyneuropathy within the Leonberger breed is a group of several genetically distinct, but clinically similar diseases. We have mapped two major genetic risk loci and identified the causative mutations that we now term LPN1 and LPN2." [From University of MN]
Breed-specific 2
Saint Bernard
Breed-specific 2 Details
Saint Bernard dogs may suffer from neuromuscular diseases collectively termed Laryngeal Paralysis and Polyneuropathy. Affected dogs may have noisy breathing, a change in their bark, and difficulty breathing due to involvement of the larynx and laryngeal folds in the throat. Additionally, they may suffer from slowly worsening exercise intolerance and develop gait abnormalities, such as an exaggerated hitched step, especially in the hind limbs. There is often wasting of the hind limb muscles as well. Eventually the disease may progress to the point where the dog cannot support its own weight and surgical intervention for laryngeal paralysis may be required. Biopsies of nerve from affected dogs show degradation of the nerve fibers and loss of myelin, the insulating material that normally helps speed messages along nerves. Muscle biopsies show atrophy resulting from nerve loss. Research carried out at the University of Minnesota, the University of Bern, and the University of California, San Diego - Comparative Neuromuscular Laboratory indicates that laryngeal paralysis and polyneuropathy within the Saint Bernard breed is a group of several genetically distinct, but clinically similar diseases. We have mapped one major genetic risk loci (originally identified in Leonberger dogs) and identified the causative mutation that we now term Leonberger Polyneuropathy type 1 (LPN1). [From University of MN]
