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Canine Mendelian disease record

Polyneuropathy with Ocular Abnormalities and Neuronal Vacuolation (Discovered in the Black Russian Terrier and Rottweiler; POANV)

Polyneuropathy with Ocular Abnormalities and Neuronal Vacuolation (Discovered in the Black Russian Terrier and Rottweiler; POANV). Autosomal recessive. Observed in 11 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 239,888 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001970-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Warburg micro syndrome 1

This is the canine counterpart of Warburg micro syndrome 1 in people. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Any Warburg micro syndrome in which the cause of the disease is a mutation in the RAB3GAP1 gene.

In humans it is also called: WARBM1, RAB3GAP1 Warburg micro syndrome, Warburg micro syndrome type 1.

MONDO:0010822 OMIM 600118

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Clinical features

In Alaskan Huskies neurological signs start at 4 to 5 months of age with visual problems. Slightly later affected dogs display an altered voice due to laryngeal paralysis, regurgitation, and gait abnormalities progressing to a severe ataxia. Dogs are typically euthanized between 8 and 16 months of age. Affected dogs have bilateral microphthalmia, small pupils, and lenses with cataract. Some affected dogs additionally exhibit strabismus and/or persistent pupillary membranes (Wiedmer et al. 2015). The Black Russian Terriers presented slightly earlier than the Alaskan Huskies at 3 months of age with laryngeal paralysis and respiratory distress. They were all euthanized by 6 months of age for severe dyspnea (Mhlanga-Mutangadura et al. 2016 (Neurobiol. Dis.) and Dennis O'Brien, personal communication).

Molecular genetics

Wiedmer et al. (2015) performed whole genome sequencing of a POANV affected Alaskan Husky. An initial automated small-scale variant analysis of the sequence data did not reveal a plausible candidate variant. Wiedmer et al. then visually inspected the short read alignments of the affected Alaskan Husky in the critical interval on chromosome 19 and identified a 218 bp SINE insertion into exon 7 of the RAB3GAP1 gene, (RAB3GAP1:c.614_615insLN864704:g.123_340). The SINE insertion was perfectly associated with the POANV phenotype in a cohort of 43 Alaskan Huskies, and it was absent from 541 control dogs of 68 other breeds. Wiedmer et al. (2015) observed that the SINE insertion leads to aberrant splicing. The mutant allele predominantly gives rise to a transcript that uses an internal splice acceptor within the SINE insertion. This mutant transcript is predicted to encode a protein, in which 39 wildtype amino acids are replaced by 46 mutant amino acids. A minor amount of transcript, in which the entire exon 7 was skipped, was observed in RNA from blood cells, but not in brain. Mhlanga-Mutangadura et al. (2016; Neurobiol. Dis.) performed whole genome sequencing at 29.3x coverage of a POANV affected Black Russian Terrier. They compared the sequence data to the genomes of 73 control dogs and identified 71 private homozygous variants in the POANV affected dog, which were predicted to alter the amino acid of a gene product. Based on a literature-based survey of the affected genes, a single base deletion in the RAB3GAP1 gene was identified as the most likely causative variant (RAB3GAP1:c.743delC). This variant was perfectly associated with the POANV phenotype in a cohort of 262 Black Russian Terriers. The variant was absent from 100 randomly selected dogs of other breeds. Mhlanga-Mutangadura et al. (2016; J. Vet. Int. Med.) reported that the c.743delC variant is also causal of the similar disorder mentioned in the History section above, namely neuronal vacuolation and spinocerebellar degeneration (NVSD; first reported by Kortz et al., 1997) in Rottweilers.

Pathology

Neuropathological examinations in affected Alaskan Huskies showed bilaterally symmetrical chronic Wallerian-type axonal degeneration in the spinal cord, which was characterized by dilated myelin sheaths containing either axonal spheroids and fragments or myelinophages. Lesions were most prominent in the superficial dorsolateral white matter tracts of the cervical and thoracic segments, where they consisted of areas of axonal and myelin loss replaced by gliotic tissue. Additionally, widely spread, bilateral-symmetrical, subtle to severe neuronal vacuolation was present in the spinal cord grey matter, facial nucleus, gracile and cuneate nuclei, vestibular nuclei, cerebellar nuclei, oculomotor nuclei, substantia nigra, thalamic nuclei, hypothalamus, hippocampus and cortex. The vacuolation was characterized by the presence of one to multiple clearly defined vacuoles of varying size in the neuronal somata and was prominent in the cerebellar nuclei. Vacuoles were also observed in the surrounding neuropil, which contained scattered axonal spheroids and was gliotic. In the cerebellar cortex, mild to severe Purkinje cell degeneration and loss were observed, associated with cerebellar atrophy in one case. Scattered axonal spheroids were present in the granule cell layer. Mild vacuolation and scattered fragmented axons were observed in the white matter of the cerebellum and brainstem. Pathological prion protein deposition was absent. In muscle and peripheral nerve biopsies from affected Alaskan Huskies, a mild variability in myofiber size with scattered atrophic fibers having an angular to anguloid shape and of both fiber types was observed. Multifocal areas of type 1 fiber grouping were observed in one of three investigated dogs. Intramuscular nerve branches were mildly to moderately depleted of myelinated fibers. Large fiber loss was evident in the peroneal and vagus nerves resulting from axonal degeneration in two of three investigated dogs. Regenerative changes were not obvious, and the vagosympathetic nerve did not reveal any specific abnormalities (Wiedmer et al. 2015). The pathological alterations in POANV affected Black Russian Terriers were similar to those seen in Alaskan Huskies. Mhlanga-Mutangadura et al. (2016; Neurobiol. Dis.) additionally found vacuoles within axons in the peripheral nerves. In electron microscopy, Mhlanga-Mutangadura et al. (2016; Neurobiol. Dis.) showed that the vacuoles were membrane bound and contained scant fibrillary debris and occasional an electron dense core of material. They did not stain with oil red O which ruled out lipid droplets. In the Purkinje cells, there were numerous small vacuoles.

History

A phenotype of neuronal vacuolation and spinocerebellar degeneration (NVSD) was initially discovered in Rottweiler dogs (Kortz et al. 1997; Andrade-Neto et al. 1998; de Lahunta and Summers, 1998; Eger et al. 1998; Vandeningh et al. 1998; Pumarola et al. 1999). Similar neurodegenerative phenotypes in combination with microphthalmia were also reported in Black Russian Terriers and Alaskan Huskies (Granger, 2011; Wiedmer et al. 2015). Variants in other genes have been associated with other forms of polyneuropathy and/or laryngeal paralysis in various breeds: OMIA 001917-9615 (ARHGEF10), OMIA 002119-9615 (GJA9), OMIA 002222-9615 (RABGEF6), OMIA 002284-9615 (SBF2), OMIA 002301-9615 (CNTNAP1). References relating to polyneuropathies and laryngeal paralysis in dogs without known genetic associations are listed under OMIA 001292-9615 and OMIA 001206-9615, respectively.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 600118 Gene · OMIM 602536

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001970-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 13.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Polyneuropathy with Ocular Abnormalities and Neuronal Vacuolation (Discovered in the Black Russian Terrier and Rottweiler; POANV) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Polyneuropathy with Ocular Abnormalities and Neuronal Vacuolation (Discovered in the Black Russian Terrier and Rottweiler; POANV) looks like in your dog's breed.
Carrier frequency by breed

Top 10 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%
Rottweiler3.1% · n 4,667
Dachshund Miniature Shorthaired<0.1% · n 579
Akita<0.1% · n 987
Bichon Frise<0.1% · n 1,055
Poodle Standard<0.1% · n 4,163
Boxer<0.1% · n 4,507
Beagle<0.1% · n 5,225
American Staffordshire Terrier<0.1% · n 42,312
Shih Tzu<0.1% · n 7,439
German Shepherd<0.1% · n 15,462
n = 86,396 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Polyneuropathy with Ocular Abnormalities and Neuronal Vacuolation (Discovered in the Black Russian Terrier and Rottweiler; POANV) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Rottweiler 3.1% 4,667
Dachshund Miniature Shorthaired <0.1% 579
Akita <0.1% 987
Bichon Frise <0.1% 1,055
Poodle Standard <0.1% 4,163
Boxer <0.1% 4,507
Beagle <0.1% 5,225
American Staffordshire Terrier <0.1% 42,312
Shih Tzu <0.1% 7,439
German Shepherd <0.1% 15,462
▸ Also observed in 1 small-sample breed (n < 50)

Frequencies in this section are statistical estimates with wide Wilson 95% confidence intervals (typically >20 percentage points). Treat these as "carriers observed but the true population frequency is not yet measurable" rather than as comparable to the well-sampled entries above.

Breed Estimate n tested
Black Russian Terrier 8.7% 23

255 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001970-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001970-9615 · Donner et al. 2023