Polyneuropathy (LPN2) - Leonberger Type
Breeds
Relevance Rating: There is some evidence or research available in this breed
General
Disease Name
Polyneuropathy (LPN2) - Leonberger Type
OMIA
2119
Gene Name
GJA9
Mutation
c.1103_1104delAG
Test Type
Genetic Disease/Disorder
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]
Details 2
"LPN2 is a partially penetrant autosomal dominant polyneuropathy resulting from a 2 base pair deletion within the gene GJA9; dogs heterozygous (D/N) and homozygous (D/D) for the LPN2 mutation may begin to show signs of disease as young as age 1, but may not show signs of disease until later in life or never at all. The average age of onset is 6 years. The identified LPN2 mutation appears to be responsible for approximately 20-25% of the cases of polyneuropathy in Leonbergers." [From University of MN)
Patents/ Licences
Research carried out at the University of Minnesota, the University of Bern, and Utrecht University has identified two LEMP mutations within the gene NAPEPLD, one in the Leonberger and the other in Rottweilers. The Rottweiler mutation has also been observed in Great Danes.
Published
A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs; Becker D, Minor KM, Letko A, et al. (2017); BMC Genomics (2017) 18:662. doi: 10.1186/s12864-017-4081-z
Published 2
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
Inheritance
ARID