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Canine Mendelian disease record

Macrothrombocytopenia (Discovered in the Norfolk and Cairn Terrier)

Macrothrombocytopenia (Discovered in the Norfolk and Cairn Terrier). Autosomal recessive. Observed in 16 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,663 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:002434-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human macrothrombocytopenia, isolated, 1, autosomal dominant

This is the canine counterpart of macrothrombocytopenia, isolated, 1, autosomal dominant 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 autosomal dominant macrothrombocytopenia in which the cause of the disease is a mutation in the TUBB1 gene.

In humans it is also called: MACTHC1, TUBB1 autosomal dominant macrothrombocytopenia.

MONDO:0800047 OMIM 613112

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.

Molecular genetics

Being aware of an earlier unpublished discovery by M.K. Boudreaux of a missense mutation in the TUBB1 gene (encoding beta1-tubulin) in several King Charles Cavalier Spaniels (CKCS) with macrothrombocytopenia, Davis et al. (2008) genotyped for this mutation in 100 CKCS dogs and 52 dogs from other breeds, for most of which platelet numbers and volume were recorded. They confirmed that a "missense mutation (c.745 G>A) in the gene encoding beta1-tubulin, predicted to result in the substitution of an asparagine for aspartic acid (D249N), correlated with the macrothrombocytopenia observed" (with thanks to Dr. Mario Van Poucke for identifying an error in an earlier version of this entry). Only one of the dogs from other breeds (a Labrador Retriever) had the same mutation (as a heterozygote). Gelain et al. (2014) reported a different missense mutation (c.5G>A; p.R2H) in the same gene (TUBB1) as the likely cause of a very similar disorder in Norfolk and Cairn Terriers.

Inheritance

From segregation analysis of 16 families of Cavalier King Charles Spaniels [CKCS] in which this disorder was segregating, Pedersen et al. (2002) concluded that " idiopathic, asymptomatic thrombocytopenia in CKCS is inherited in an autosomal recessive manner. The condition most likely constitutes an inherited macrothrombocytopenia in dogs".

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 613112 Gene · OMIM 612901

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002434-9615, 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 9.

  6. Giant platelet disorder in the Cavalier King Charles Spaniel. · Exp Hematol · 2004 · PMID 15050744

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 Macrothrombocytopenia (Discovered in the Norfolk and Cairn Terrier) 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 Macrothrombocytopenia (Discovered in the Norfolk and Cairn Terrier) looks like in your dog's breed.
Carrier frequency by breed

Top 14 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%15%30%
Cairn Terrier19.4% · n 183
Chesapeake Bay Retriever4.0% · n 138
Danish Swedish Farmdog0.82% · n 61
Kromfohrlander0.76% · n 197
Parson Russell Terrier0.55% · n 181
West Highland White Terrier0.30% · n 658
Chihuahua<0.1% · n 4,273
Poodle Miniature<0.1% · n 3,555
German Shepherd<0.1% · n 15,648
Yorkshire Terrier<0.1% · n 8,367
Pug<0.1% · n 5,154
Golden Retriever<0.1% · n 12,881
Labrador Retriever<0.1% · n 16,856
American Staffordshire Terrier<0.1% · n 42,793
n = 110,945 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 Macrothrombocytopenia (Discovered in the Norfolk and Cairn Terrier) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Cairn Terrier 19.4% 183
Chesapeake Bay Retriever 4.0% 138
Danish Swedish Farmdog 0.82% 61
Kromfohrlander 0.76% 197
Parson Russell Terrier 0.55% 181
West Highland White Terrier 0.30% 658
Chihuahua <0.1% 4,273
Poodle Miniature <0.1% 3,555
German Shepherd <0.1% 15,648
Yorkshire Terrier <0.1% 8,367
Pug <0.1% 5,154
Golden Retriever <0.1% 12,881
Labrador Retriever <0.1% 16,856
American Staffordshire Terrier <0.1% 42,793
▸ Also observed in 2 small-sample breeds (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
Norfolk Terrier 47.1% 17
Caucasian Shepherd Dog 2.4% 41

250 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
3
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:002434-9615.

  • 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:002434-9615 · Donner et al. 2023