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Canine Mendelian disease record

Mucopolysaccharidosis, Type VII (Discovered in the German Shepherd Dog; MPS VII)

Mucopolysaccharidosis, Type VII (Discovered in the German Shepherd Dog; MPS VII). Autosomal recessive. Observed in 3 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:000667-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human mucopolysaccharidosis type 7

Dogs with this condition carry a change in GUSB. In people, changes in the same gene cause mucopolysaccharidosis type 7. 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: Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease belonging to the group of mucopolysaccharidoses.

In humans it is also called: MPS7, MPSVII, Beta-glucuronidase deficiency, beta-glucuronidase deficiency, MPS VII.

MONDO:0009662 OMIM 253220

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

Mucopolysaccharidosis VII is a lysosomal storage disease characterized by accumulation of undegraded glycosaminoglycans (dermatan, heparan, and chondroitin sulfates) in lysosomes. Clinical signs include facial dysmorphia, diffuse corneal clouding, appendicular and axial skeletal lesions, and glycosaminoglycans in urine. Affected animals are deficient in the enzyme beta-glucuronidase, which is a lysosomal acid hydrolase. Affected animals have very low enzyme activity compared to normal animals, and carriers have 40-60% enzyme activity compared to normal animals. The mode of inheritance is autosomal recessive. The causative mutation is a G to A substitution in the gene coding for the hydrolase, beta-glucuronidase (GUSB). There is a test available to detect the causative mutation. Testing siblings of affected dogs is recommended. Breeding of carriers or affected dogs is not recommended. Edited by Mark Haskins, VMD, Ph.D

Clinical features

At 4 weeks of age, affected dogs show a shortened, broad face, low-set ears, and a laterally broad chest. By 8 weeks of age, diffuse corneal clouding is apparent. At 9 weeks of age, affected dogs are half as large as their normal littermates, but have disproportionately large heads. Polymorphonuclear leukocytes and lymphocytes from affected animals contain coarse cytoplasmic granules that stain with toluidine blue. Urine from affected animals contain excessive chondroitin 4- and 6-sulfates and dermatan and heparan sulfates. By 2 to 5 months of age, affected dogs have trouble standing but can move in sternal recumbency. Most joints are easily subluxated and crepitant, with swollen, fluctuant joint capsules filled with excessive synovial fluid. There is significant epiphyseal dysplasia. Cardiac abnormalities, primarily mitral insufficiency and aortic aneurism can be present but are variable (Haskins et al., 1991).

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans and other mammals), Ray et al. (1998; Genomics 48:248-253) identified the initial causative mutation as a "guanosine to adenine base change at nucleotide position 559 in the canine cDNA sequence [that] causes an arginine to histidine substitution at amino acid position 166" of the gene coding for hydrolase beta-glucuronidase (GUSB). In Brazilian Terriers, Hytönen et al. (2012) sequenced the entire 13Mb candidate region from their GWAS (see Mapping section), and discovered that the disorder in this breed is due to a "missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB)".

Pathology

Affected animals are deficient in the enzyme beta-glucuronidase, which is a lysosomal acid hydrolase. Affected animals have very low enzyme activity compared to normal animals, and carriers have 40-60% enzyme activity compared to normal animals. Signs are caused by accumulation of undegraded glycosaminoglycans in lysosomes (Ray et al., 1999). Affected animals exhibit a misshapen and narrowed trachea, thickening of the AV heart valve leaflets and chordae tendinae, thickened aortic arch, hyperplasia of synovial membranes, and erosion of the articular cartilage (Haskins et al., 1991). Cytoplasmic vacuoles are evident in neurons of the central nervous system, hepatocytes, Kupffer cells, keratocytes, retinal pigment epithelium, AV heart valve fibroblasts, aortic smooth muscle cells, leukocytes, chondrocytes, and synovial cells. These vacuoles are either empty or contain granular or lamellar material (Haskins et al., 1991).

Control

Testing siblings of affected dogs is recommended. Breeding of carriers or affected dogs is not recommended.

Genetic testing

There is a test available to detect the causative mutation.

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 253220 Gene · OMIM 611499

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000667-9615, 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 mucopolysaccharidosis type 7 (MONDO:0009662).

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 42.

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 Mucopolysaccharidosis, Type VII (Discovered in the German Shepherd Dog; MPS VII) 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 Mucopolysaccharidosis, Type VII (Discovered in the German Shepherd Dog; MPS VII) looks like in your dog's breed.
Carrier frequency by breed

Top 2 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%1%2%
German Shepherd<0.1% · n 15,648
American Staffordshire Terrier<0.1% · n 42,793
n = 58,441 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 Mucopolysaccharidosis, Type VII (Discovered in the German Shepherd Dog; MPS VII) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
German Shepherd <0.1% 15,648
American Staffordshire Terrier <0.1% 42,793
▸ 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
Terrier Brazileiro 10.0% 5

263 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
1
Phenotype confirmed
1
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:000667-9615.

  • 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:000667-9615 · Donner et al. 2023