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Greyhound Polyneuropathy (GHPN)
| Acronym: | GHPN, NDRG1 |
| Gene: | NDRG1 |
| Mutation: | c.1080_1089delTCGCCTGGAC |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Greyhound Polyneuropathy (GHPN) 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, including Great Dane, Rottweiler, Dalmatian, Alaskan Malamute, etc. Canine polyneuropathies share many similarities with the Charcot-Marie-Tooth (CMT) group of diseases in humans. Polyneuropathy in literal translation means “many abnormalities of the nervous system”. The Greyhound breed before was primarily used as a racing dog, until the 1960s, when the breed was separated into show dogs and racing dogs. Researchers confirmed a high inbreeding rate between Greyhound show dogs and revealed that all polyneuropathy-affected dogs (GHPN) were related to a single popular sire born in 1968. Greyhound Polyneuropathy (GHPN) is a neurodegenerative disorder with juvenile age of onset. Clinical signs appear between three to nine months of age. Owners of affected dogs already in early stages notice exercise intolerance and difficulties during walking, such as high stepping gait and bunny hopping. The gait appears as moderately to markedly ataxic, depending on the stage of disease, and appeared short-stride. After exercise shaking and collapse appears. As the disorder progresses, severe muscle atrophy, ataxia, and dysphonia (voice disorders) develop. Reduction in muscle tone varies from moderately to severely, and a lack of resistance to passive joint movement in either direction is present. Myotatic reflexes are reduced or absent. In the terminal stages of the disorder, cranial nerve function becomes affected. No behavioral changes have been reported, and affected dogs appear alert, bright, and responsive. Neurological symptoms are delayed reactions, hyporeflexia, distal limb muscle atrophy, and inspiratory stridor. Motor and sensory nerve conductions become reduced.
Pathological findings show mild to a marked reduction in myelinated nerve fiber density as well as hyperplasia of the axon-Schwann cell network in about 10% of large myelinated fibers. Neurogenic atrophy was present within skeletal muscles, which varied in its severity between affected dogs. After the appearance of the clinical signs, affected dogs usually do not survive longer than ten months and commonly euthanasia is required due to humane reasons. Greyhound Polyneuropathy (GHPN) is caused by a deletion in the NDRG1 gene. The prevalence of the mutation is high among the show dog population of greyhounds, where 25% of the tested dogs are revealed as carriers. GHPN 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.
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:
Drögemüller C et al. A Deletion in the N-Myc Downstream Regulated Gene 1 (NDRG1)Gene in Greyhounds with Polyneuropathy PLoS One. 2010 Jun 22;5(6):e11258.