Test Detail

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.

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.

- Progressive ataxia of juvenile onset\n- Voice change due to laryngeal paralysis\n- Regurgitation and dysphagia (megaesophagus)\n- Ocular abnormalities and microphthalmia (more typical of POANV)\n- Progressive neurological deterioration

Neuronal vacuolation and spinocerebellar degeneration in the Rottweiler were described in the 1990s. Mhlanga-Mutangadura et al. (2016) identified the RAB3GAP1 c.743delC mutation in Rottweilers with NVSD and, in parallel, in Black Russian Terriers with polyneuropathy and neuronal vacuolation, enabling a DNA test.

- 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

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

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