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Leonberger Polyneuropathy 2 (LPN2)
| Acronym: | LPN2 |
| Gene: | GJA9 |
| Mutation: | c.1107_1108delAG |
| Inheritance: | Autosomal dominant with incomplete penetrance |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
| Method: |
Genetics and characteristics
Leonberger Polyneuropathy 2 (LPN2) is a form of neuropathy affecting this dog breed. It differs from another form of polyneuropathy affecting Leonbergers by a causative mutation. Polyneuropathy is a term used for simultaneous malfunction of many peripheral nerves throughout the body and in literal translation, it means “many abnormalities of the nervous system”. Other dog breeds affected by PN are Greyhounds, Alaskan Malamute, Black Russian Terriers, Rottweilers, and Alaskan Husky Dogs. Polyneuropathy observed in Leonbergers shows similar clinical symptoms to Charcot-Marie-Tooth (CMT) in humans. Charcot-Marie-Tooth (CMT) is a genetically heterogeneous group of neuropathies that cause damage to peripheral nerves. CMT is the most common inherited disorder of peripheral nerves in humans.
Affected Leonbergers show abnormal motor signs, such as weakness, hypotonia, and muscle atrophy due to denervation. Other symptoms include laryngeal paralysis, a change in the bark, inspiratory stridor, and dyspnea. The age of LPN onset is variable, from less than 1 year of age to 11 years of age. Dogs affected with an early onset of the disorder usually develop more severe symptoms and stages of the disorder. Since Leonberger Polyneuropathy (LPN2) is a progressive disorder, owners in its beginning stages may not even notice the first symptoms, such as unbalanced walking. It is common that veterinarians are not able to recognize the disorder before the already progressed stages.
Leonberger Polyneuropathy (LPN2) is caused by a deletion mutation in the GJA9 gene. This gene encodes for gap junction protein alpha 9, which is a type of connexin. It is involved in the formation of gap junctions, connections between cells that directly connect the cytoplasms of contacting cells. LPN2 is inherited in a dominant inheritance pattern with incomplete penetrance. Another form of polyneuropathy has been also recognized in Leonberger dogs, known as LPN, which is caused by a different mutation, in a different gene.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Becker D. et al (2017): A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs. MC Genomics 18:662.
Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, et al. (2014) An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs. PLoS Genet 10(10): e1004635. doi:10.1371/journal.pgen.1004635