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Juvenile Laryngeal Paralysis & Polyneuropathy (JLPP)
| Acronym: | JLPP |
| Gene: | RAB3GAP1 |
| Mutation: | c.743delC |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Juvenile Laryngeal Paralysis and Polyneuropathy (JLPP) is a neurological disorder that has been discovered in Black Russian Terriers. As a disorder affecting the nerves, it is named polyneuropathy: poly- (many), neuro- (nerves), -pathy (a disease). It is the most common disorder in the Black Russian Terrier breed. The disorder appears to be similar to Charcot Marie Tooth disease which affects humans. The same as in Charcot Marie Tooth disease, Juvenile Laryngeal Paralysis, and Polyneuropathy in dogs appear as very heterogeneous, from predominantly demyelinating forms to predominantly axonal forms. Predominantly demyelinating forms are characterized by very slow motor nerve conduction velocities (MNCV) and histopathological evidence of demyelination. Predominantly axonal forms are characterized by mildly slowed MNCV and axonal abnormalities on histopathology with many intermediate forms.
The first symptoms of the disease appear in the larynx and throat. In a healthy dog, one of the longest nerves in the body supplies the muscles of the voice box, called the larynx. While the dog is barking, air moves over the vocal folds, which start to vibrate. On the other hand, when the dog breathes in, the larynx’s muscles pull the vocal folds to the side, so the air can easily enter the lungs. When the nerves are unable to transmit this message correctly, the muscles become weak or even paralyzed. The dog is unable to breathe in properly, due to a vocal fold that cannot be pulled out of the way. This is called laryngeal paralysis, and it is often the first symptom in the affected dogs. Affected dogs breathe noisily, and the airflow into the lungs is particularly difficult during the dog’s exercise or in hot weather. Choking on food or water is common, which often results in pneumonia. Abnormalities in the eye development of the affected dogs have been also reported. JLPP-affected dogs appear to have smaller eyes than normal, a condition called microphthalmia, and they develop cataracts as well as other changes.
Juvenile Laryngeal Paralysis and Polyneuropathy (JLPP) is caused by a mutation in the RAB3GAP1 gene. The disorder is inherited in an autosomal recessive manner. In case of showing the JLPP symptoms, the healthy parents of the affected cub are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. 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. There is no cure for this disorder, 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 to do 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:
Mhlanga-Mutangadura, T., Johnson GS. (2016): A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs. Neurobiol Dis. Feb;86:75-85.
Mhlanga-Mutangadura, T., Johnson, G. S., Johnson, G. C., Hansen, L., Tamassia, O’Brien, D. P., et al. (2014): The whole genome sequences from a Rottweiler and Black Russian Terrier with overlapping neurological syndromes contain the same RAB3GAP1 frame shift mutation.