Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612901 (gene) , 613112 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

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".

Molecular basis: Being aware of an earlier unpublished discovery by M.K. Boudreaux of a missense mutation in the TUBB1 gene (encoding beta1-tubulin) in several King Charles Cavalier Spaniels (CKCS) with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.

Breeds: Cairn Terrier (Dog) (VBO_0200267), Cavalier King Charles Spaniel (Dog) (VBO_0200309), Norfolk Terrier (Dog) (VBO_0200945).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).