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Canine Mendelian disease record

GM2 Gangliosidosis (Discovered in the Toy Poodle)

GM2 Gangliosidosis (Discovered in the Toy Poodle). Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,665 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier
OMIA:001462-9615
Autosomal recessive
Linked gene
HEXB
Human counterpart
In humans, this gene is HEXB. OMIM 606873 In people, HEXB appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 1.09). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms. In people, variants in the HEXB gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Sandhoff disease

Dogs with this condition carry a change in HEXB. In people, changes in the same gene cause Sandhoff disease. 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: A lysosomal disorder from the GM2 gangliosidosis family, caused by biallelic pathogenic variants in the HEXB gene, characterized by GM2 ganglioside accumulation in the nervous system and progressive central nervous system degeneration.

In humans it is also called: GM2 gangliosidosis 0 variant, GM2 gangliosidosis, 0 variant, Hexosaminidases A and B deficiency, Sandhoff Jatzkewitz disease.

MONDO:0010006 OMIM 268800 Mechanism (DisMech) →

Human mechanism pathograph for Sandhoff Disease is curated in DisMech (Monarch Initiative), joined by exact Mondo id. That page is about people. It is not a treatment plan for a dog.

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.

Summary

Also known as Sandhoff disease and GM2 gangliosidosis variant 0. A lysosomal storage disease in which there is a buildup (storage) of GM2 gangliosides (a type of glycolipid) in various tissues, due to the lack of the enzyme hexosaminidase, whose task is to break down the GM2 ganglioside into its constituents. Characterised by progressive neuromuscular dysfunction and impaired growth from an early age.

Molecular genetics

Rahman et al. (2012) reported the causal mutation in Toy Poodles as being a "single base pair deletion of guanine in exon 3 [of the canine HEXB gene] was identified at nucleotide position 283 of the putative open reading frame (c.283delG). This mutation has the potential to cause a frameshift resulting in the alteration of valine at amino acid position 59 to a stop codon (p.V59fsX)." This is the first published report of a causal mutation for this disorder in dogs. Kolicheski et al. (2017) reported that a likely causal variant in the Shiba Inu breed is "chr2:57,243,656_57,243,658delCCT (CanFam 3.1)". Wang et al. (2018) reported a "3‐base pair deletion in the HEXB gene (c.618‐620delCCT)" as the likely causal variant in an affected Shiba Inu dog.

Prevalence

Kolicheski et al. (2017): "To estimate the frequency of the 3-bp HEXB deletion among the Shiba Inu, all 40 Shiba Inu represented in the University of Missouri DNA repository were genotyped by PCR-RFLP for this deletion. Thirty-seven of the tested Shiba Inu were homozygous for the reference allele; the other 3 were heterozygotes. These heterozygotes were born in 2002, 2004, and 2007. There are no known familial relationships among them or between them and the 2 affected Shiba Inu described here. This observation suggests that the 3-bp HEXB deletion may be rare but widely distributed in the Shiba Inu breed."

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 268800 Gene · OMIM 606873

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001462-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as Sandhoff disease (MONDO:0010006).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (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 11.

  3. Animal models of GM2 gangliosidosis: utility and limitations. · Appl Clin Genet · 2016 · PMID 27499644
  5. GM2 gangliosidosis variant 0 (Sandhoff Disease) in a mixed-breed dog. · J Am Anim Hosp Assoc · 2015 · PMID 26535459

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.

Your breed

See what GM2 Gangliosidosis (Discovered in the Toy Poodle) looks like in your dog's breed.
Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency 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.

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 variant 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:001462-9615.

  • 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:001462-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)