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Canine Mendelian disease record

GM2 Gangliosidosis (Discovered in the Japanese Chin)

GM2 Gangliosidosis (Discovered in the Japanese Chin). Autosomal recessive. Observed in 1 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:001461-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Tay-Sachs disease

This is the canine counterpart of Tay-Sachs disease 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: GM2 gangliosidosis, variant B or Tay-Sachs disease is marked by accumulation of G2 gangliosides due to hexosaminidase A deficiency.

In humans it is also called: TSD, B variant GM2 gangliosidosis, disease, Tay-Sachs, gangliosidosis GM2, type 1, GM2 gangliosidosis, B, B1 variant.

MONDO:0010100 OMIM 272800

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

GM2 gangliosidos is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. Mutations in the HEXA gene cause type I (or "type B") GM2 gangliosidosis, also called Tay-Sachs disease in humans. In dogs the age of onset is between 1 and 2 years and affected dogs exhibit progressive cerebellar ataxia, altered mental status and vision deficits. The disease is progressive and leads to death or requires euthanasia within a few months.

Molecular genetics

GM2 gangliosidosis, type I in Japanese Chin dogs is most likely caused by the c.967G>A variant in the HEXA gene, which leads to the p.E323K substitution. The wildtype glutamate at position 323 is part of the catalytically active site of hexosaminidase, Therefore, the variant is predicted to result in a complete loss of enzymatic activity (Sanders et al. 2013). Genotyping one of the two cases in this same breed for the c.967G>A variant provided supporting evidence for the causality of this variant (Freeman et al., 2013).

Pathology

Freeman et al. (2013) reported " the first MRI description of the B variant of GM2 gangliosidosis in 2 Japanese Chin dogs".

History

In 1985 a GM2 gangliosidosis in Japanese Spaniels or Japanese Chin dogs was described clinically and histopathologically (Cummings et al. 1985). Recently, two new cases were carefully diganosed clinically and histopathologically. The biochemical analysis of the storage material clearly indicated a GM2 gangliosidosis. The sequence analysis of the candidate gene HEXA revealed a highly plausible candidate causative mutation, which was perfectly associated with the phenotype (Sanders et al. 2013)

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 272800 Gene · OMIM 606869

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001461-9615, 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.

  1. Animal models of GM2 gangliosidosis: utility and limitations. · Appl Clin Genet · 2016 · PMID 27499644
  5. GM2 gangliosidosis in a Japanese spaniel. · Acta Neuropathol · 1985 · PMID 2931941

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 GM2 Gangliosidosis (Discovered in the Japanese Chin) 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 GM2 Gangliosidosis (Discovered in the Japanese Chin) looks like in your dog's breed.
Carrier frequency by breed

Top 1 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%5%10%
Japanese Chin3.2% · n 78
n = 78 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 GM2 Gangliosidosis (Discovered in the Japanese Chin) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Japanese Chin 3.2% 78

265 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:001461-9615.

  • 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:001461-9615 · Donner et al. 2023