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Alaskan Malamute Polyneuropathy (AMPN)
| Acronym: | AMPN |
| Gene: | NDRG1 |
| Mutation: | c.293G>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Alaskan malamute polyneuropathy (AMPN) is a disorder that belongs to a wider group of disorders known as polyneuropathies. Inherited neuropathies until now have been recognized in 22 dog breeds and share many similarities with the Charcot-Marie-Tooth (CMT) group of diseases in humans. Charcot-Marie-Tooth is clinically characterized by muscle weakness and sensory loss. Polyneuropathy in literal translation means “many abnormalities of the nervous system”. The first symptoms of Alaskan malamute polyneuropathy usually occur in seven to 18 months old dogs. The disorder appears in both sexes. Clinical symptoms are exercise intolerance, pelvic limb ataxia, loss of muscle mass, changes in voice due to an affected larynx, problems while swallowing, and lack of coordination. More detailed examinations revealed decreased postural reactions, decreased or completely absent spinal reflexes, laryngeal paresis, and muscle atrophy. The severity of symptoms may vary, from mild to severe. In the affected dogs, it has been noticed that symptoms appear suddenly, rather than gradually and progressively. In some dogs, it has been reported a period of six to eight months of more severe symptoms which afterward lessen but do not disappear completely. Symptoms in some dogs appear so severe that euthanasia is required.
Alaskan malamute polyneuropathy (AMPN) is caused by a point mutation in the NDRG1 gene. AMPN is inherited in an autosomal recessive pattern. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of polyneuropathy. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Until now, no treatment for the Alaskan malamute polyneuropathy (AMPN) has been developed, and the only way to prevent it is to breed dogs that are not carriers of the mutation. Defected genes for autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. The only way to find out if there is a chance of getting an affected puppy is through genetic testing.
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. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not 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.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Bruun CS, Jäderlund KH, Berendt M, Jensen KB, Spodsberg EH, et al. (2013): A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy. PLoS ONE 8(2): e54547. doi:10.1371/journal.pone.0054547
Drögemüller C et al. (2010.): A Deletion in the N-Myc Downstream Regulated Gene 1 (NDRG1)Gene in Greyhounds with Polyneuropathy PLoS One. 2010 Jun 22;5(6):e11258.
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