Macrothrombocytopenia, congenital

 

Gene: TUBB1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

King Charles Terrier mutation: Substitution, TUBB1 gene; c.745 G>A, p.(D249N), exon5

Cairn Terrier mutation: Substitution, TUBB1 gene; c.5 G>A, p.(R2H)

Medical system: Blood

Breeds: American Staffordshire Terrier/Amstaff, Cairn Terrier, Caucasian Shepherd Dog, Chesapeake Bay Retriever, Chihuahua, Danish Swedish Farmdog, German Shepherd, Golden Retriever, Kromfohrlander, Labrador Retriever, Norfolk Terrier, Poodle - Miniature (Dwarf), Pug, West Highland White Terrier, Yorkshire Terrier

Age of onset of symptoms: At birth

Congenital macrothrombocytopenia is a genetic blood condition that is seen in several breeds of dog and has a particularly high prevalence in Cavalier King Charles Spaniels.  Affected dogs have fewer and larger platelets than normal, however this does not lead to problems with coagulation or bleeding.  This condition can be confused with acquired thrombocytopenia caused by infections or immune problems, resulting in a false diagnosis that can lead to unnecessary treatments with antibiotics or anti-inflammatories.

 

References:

OMIA links: [1001-9615], [2434-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Gelain ME, Bertazzolo W, Tutino G, et al. (2014) A novel point mutation in the beta1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers.  Vet Clin Pathol. 43(3):317-21. [pubmed/25060661]

Gelain ME, Tutino GF, Pogliani E, Bertazzolo W. (2010) Macrothrombocytopenia in a group of related Norfolk terriers. Vet Rec 167:493-4. [pubmed/20871084]

Davis B, Toivio-Dinnucan M, Schuller S, Boudreaux MK. (2008) Mutation in Beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels.  J Vet Int Med 22:540-545. [pubmed/18466252]