Thrombocytopenia (TUBB1 gene)

Thrombocytopenia is a disorder in which a decrease in platelet count is observed. A mutation has been identified in the gene encoding β1-tubulin that is associated with the occurrence of thrombocytopenia.

Symptoms

Dogs with thrombocytopenia are usually asymptomatic, with symptoms occurring when the platelet count is dangerously low. Common clinical signs include blood loss, fever, bruising, weakness, hematuria, sudden collapse or excessive coughing.

Disease Management

When low platelet counts are the primary problem, a blood or platelet transfusion may be considered to directly address the thrombocytopenia. However, if this condition is a symptom of a more serious underlying disease, the focus of treatment will be on addressing and controlling the underlying cause.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The TUBB1 gene is responsible for encoding the β1-tubulin protein, which is a component of microtubules in megakaryocytes, the precursor cells of platelets. Microtubules are essential elements of the cytoskeleton that provide structural function. In the King Charles Spaniel breed, a nonsense mutation (c.745G>A) has been identified in the TUBB1 gene involving the substitution of an asparagine for aspartic acid in β1-tubulin. The change produced seems to affect the assembly of microtubules, which hinders the proper formation of proplatelets, and consequently of platelets. This would explain the reduction in platelet count characteristic of thrombocytopenia. In the Cairn Terrier and Norfolk Terrier breeds, a different nonsense mutation (c.5G>A) in the same TUBB1 gene has been described as a causative variant of thrombocytopenia. However, to date, this variant is not yet included in our test.

Most affected breeds

King Charles Spaniel

Bibliography

Davis B, Toivio-Kinnucan M, Schuller S,et al. Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med. 2008 May-Jun;22(3):540-5.

Gelain ME, Bertazzolo W, Tutino G,et al. A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers. Vet Clin Pathol. 2014 Sep;43(3):317-21.