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Canine Mendelian disease record

Neuroaxonal Dystrophy (Discovered in the Rottweiler; VPS11-related)

Neuroaxonal Dystrophy (Discovered in the Rottweiler; VPS11-related). Autosomal recessive. Observed in 7 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 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:002152-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human hypomyelinating leukodystrophy 12

This is the canine counterpart of hypomyelinating leukodystrophy 12 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 leukodystrophy in which the cause of the disease is a mutation in the VPS11 gene.

In humans it is also called: HLD12, hypomyelinating leukodystrophy type 12, leukodystrophy caused by mutation in VPS11, leukodystrophy, hypomyelinating, 12, leukodystrophy, hypomyelinating, type 12.

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

Lucot et al. (2018):"Rottweiler NAD was first reported in the early 1980s and is characterized by a young adult age of onset with mild progression of clinical signs, typically including postural deficits, ataxia, hypermetria, intention tremor and nystagmus". Some clinical signs will develop at an older age (3-5 years old), these include head bobbing, head tremor, nystagmus and menace deficit (Chrisman, 1992). [IT thanks DVM student Hedia Chan for contributions to this entry in April 2022]

Molecular genetics

Lucot et al. (2018): "Whole-genome sequencing of two histopathologically confirmed canine NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T>C; p.H835R) that was associated with the phenotype".

Pathology

Lucot et al. (2018): “Clinical signs reflect the predominantly sensory topographical distribution of pathology within the central nervous system, (CNS) consisting of mild cerebellar atrophy, large number of axonal spheroids, and demyelination of axons in the vestibular nucleus, lateral and medial geniculate nuclei sensory nucleus of the trigeminal nerve, gracilis and cuneate nuclei, and in the spinal cord dorsal horn.”

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.

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002152-9615, 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 8.

  1. Phenotypic and genetic aspects of hereditary ataxia in dogs. · J Vet Intern Med · 2023 · PMID 37341581
  2. Neuroaxonal dystrophy in a Rottweiler pup. · J Am Vet Med Assoc · 1988 · PMID 3410773

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 Neuroaxonal Dystrophy (Discovered in the Rottweiler; VPS11-related) 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 Neuroaxonal Dystrophy (Discovered in the Rottweiler; VPS11-related) looks like in your dog's breed.

Carrier frequency by breed

Top 7 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%
Rottweiler3.0% · n 4,718
Chow Chow0.31% · n 643
Boxer<0.1% · n 4,557
Beagle<0.1% · n 5,292
German Shepherd<0.1% · n 15,648
Labrador Retriever<0.1% · n 16,856
n = 90,507 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 Neuroaxonal Dystrophy (Discovered in the Rottweiler; VPS11-related) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Rottweiler 3.0% 4,718
Chow Chow 0.31% 643
Boxer <0.1% 4,557
American Staffordshire Terrier <0.1% 42,793
Beagle <0.1% 5,292
German Shepherd <0.1% 15,648
Labrador Retriever <0.1% 16,856

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

Penetrance

From genotype to phenotype

Carrier status is not the same as disease status. Penetrance is the fraction of at-risk dogs that develop the phenotype. The Donner 2023 S4 table tracks this for 1 variant(s) underlying this disease in the cohort.

At-risk dogs evaluated
2
Phenotype confirmed
2
Penetrance range
not yet quantifiable

Fewer than 20 at-risk dogs evaluated; too few to state a penetrance figure.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome is governed by 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:002152-9615.

  • 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:002152-9615 · Donner et al. 2023