Polyneuropathy, Neuronal Vacuolation and Spinocerebellar Degeneration, NVSD, POANV

 

Gene: RAB3GAP1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutations:

Black Russian Terrier, Rottweiler mutation: Deletion, RAB3GAP1 gene; c.743 del.C, p.(P248 L fs STOP 4), exon7

Alaskan Husky insertion: Insertion (SINE), RAB3GAP1 gene; c.614_615 ins 218 nt

Medical system: Neurological

Breeds: Akita, American Staffordshire Terrier/Amstaff, Bichon Frise, Black Russian Terrier, Boxer, Dachshund Miniature Longhair/Shorthair, Dachshund Standard Longhair/Shorthair, German Shepherd, Poodle - Standard, Rottweiler, Shih Tzu

Age of onset of symptoms: Juvenile animal (2 to 4 months)

Polyneuropathy is a general term for a family of hereditary diseases of nerves and nerve cells that can affect dogs.   These diseases can involve a number of mutations in a number of genes, some that are known and many that are not as yet characterized.  Neuronal Vacuolation, Spinocerebellar Degeneration (NVSD) is a polyneuropathy seen in young (2 to 4-month-old) Rottweiler and Black Russian Terrier puppies that is caused by a recessive mutation in the RAB3GAP1 gene.  The dogs show signs of respiratory distress due to laryngeal paralysis and additional symptoms including ataxia and reduced spinal reflexes.  Also, there can be problems with eye development including microphthalmia, cataracts and miotic pupils.  When nerves examined histologically, there are vacuoles within the nerve cell bodies and within axons.  There is no treatment for the disease which carries a poor prognosis.  The best approach for controlling NVSD is to identify carrier animals and to perform matings to avoid producing double mutant puppies.

 

References:

OMIA link: [1970-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Mhlanga-Mutangadura T, Johnson GS, Schnabel RD, Taylor JF, et al. (2016) A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with poyneuropathy and neuronal vacuolation in Black Russian Terrier dogs.  Neurobiology of Disease 86:75-85. [pubmed/26607784]

Mhlanga-Mutangadura T, Johnson GS,Ashwini GD, Shelton GD, et al. (2016) A homozygous RAB3GAP1:c.743delC mutation in Rottweilers with neuronal vacuolation and spinocerebellar degeneration.  J. Vet. Intern. Med 30:813-818. [pubmed/26968732]

Wiedmer M, Oevermann A, Borer-Germann SE, et al. (2015) A RAB3GAP1 SINE Insertion in Alaskan Huskies With Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1). G3 (Bethesda). 6(2):255-62. [pubmed/26596647]

Granger N. (2011) Canine inherited motor and sensory neuropathies: an updated classification in 22 breeds and comparison to Charcot-Marie-Tooth disease. Vet J. 188(3):274-85. [pubmed/20638305]