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Juvenile laryngeal paralysis and polyneuropathy (JLPP)

Neurological · Dog

Inherited neurodegenerative disease of juvenile onset caused by biallelic variants of RAB3GAP1, a membrane trafficking gene. In the Rottweiler it presents as neuronal vacuolation and spinocerebellar degeneration (NVSD) and in the Black Russian Terrier as polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV/JLPP), with the same c.743delC allele. It is characterized by ataxia, voice change due to laryngeal paralysis and regurgitation.
Inheritance patternAutosomal recessive (OMIA:001970-9615); affected dogs are homozygous for c.743delC
Gene / MutationRAB3GAP1 c.743delC (frameshift); allele shared between the Rottweiler (NVSD) and the Black Russian Terrier (POANV/JLPP). OMIA:001970-9615
PenetranceHomozygotes develop the disease; in the Rottweiler series the cases confirmed by necropsy were homozygous (Mhlanga-Mutangadura et al. 2016). No quantitative estimate of penetrance.
Codeoirk
Turnaround time10 days
Price52,60 €

Incidence

The c.743delC allele is documented in the Rottweiler (NVSD) and the Black Russian Terrier (POANV); the Alaskan Husky has a different SINE insertion in RAB3GAP1 (Wiedmer et al. 2015). No published population prevalence figures.

Breeder management

- Test breeders of the affected breeds before mating\n- Autosomal recessive inheritance: do not use affected homozygotes as breeders\n- Do not cross two carriers (25 % homozygotes per litter)\n- A carrier may be crossed with a clear dog; test the offspring intended for breeding\n- Record the status in the pedigree

Specialist notes

Differential diagnosis with other hereditary laryngeal paralyses/polyneuropathies (ARHGEF10, GJA9, RAPGEF6, SBF2, CNTNAP1). Confirm with genotyping and, if appropriate, histopathological study (neuronal vacuolation).

References

Mhlanga-Mutangadura T et al. 2016. A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration. J Vet Intern Med. PMID: 26968732; Mhlanga-Mutangadura T et al. 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. PMID: 26607784; Wiedmer M et al. 2015. A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV). G3 (Bethesda). PMID: 26596647

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