OMIA:002434-9615 : Thrombocytopenia, TUBB1-related in Canis lupus familiaris
Categories: Haematopoietic system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: 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Molecular basis: Being aware of an earlier unpublished discovery by M.K. Boudreaux of a missense mutation in the TUBB1 gene (encoding beta1-tubulin) in several King Charles Cavalier Spaniels (CKCS) with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, Cavalier King Charles Spaniel, Norfolk Terrier.
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|98||Cairn Terrier Norfolk Terrier||Thrombocytopaenia||TUBB1||missense||Naturally occurring variant||CanFam3.1||24||g.43761303G>A||c.5G>A||p.(R2H)||XM_022408906.1; XP_022264614.1||2014||25060661||Genomic coordinates in CanFam3.1 provided by Zoe Shmidt and Robert Kuhn.|
|81||King Charles Spaniel||Thrombocytopaenia||TUBB1||missense||Naturally occurring variant||CanFam3.1||24||g.43766144G>A||c.745G>A||p.(D249N)||XM_022408906.1; XP_022264614.1||rs1152388419||2008||18466252||Sequence information used to identify the genomic location was kindly provided by Mary K Boudreaux.|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :|
|Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787 . DOI: 10.1186/s13059-023-03023-7.|
|2014||Gelain, M.E., Bertazzolo, W., Tutino, G., Pogliani, E., Cian, F., Boudreaux, M.K. :|
|A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers. Vet Clin Pathol 43:317-21, 2014. Pubmed reference: 25060661 . DOI: 10.1111/vcp.12168.|
|2010||Gelain, M.E., Tutino, G.F., Pogliani, E., Bertazzolo, W. :|
|Macrothrombocytopenia in a group of related Norfolk terriers. Vet Rec 167:493-4, 2010. Pubmed reference: 20871084 . DOI: 10.1136/vr.c4782.|
|2008||Davis, B., Toivio-Kinnucan, M., Schuller, S., Boudreaux, MK. :|
|Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 22:540-5, 2008. Pubmed reference: 18466252 . DOI: 10.1111/j.1939-1676.2008.0085.x.|
|2005||Singh, MK., Lamb, WA. :|
|Idiopathic thrombocytopenia in Cavalier King Charles Spaniels. Aust Vet J 83:700-3, 2005. Pubmed reference: 16315671 .|
|2004||Cowan, SM., Bartges, JW., Gompf, RE., Hayes, JR., Moyers, TD., Snider, CC., Gerard, DA., Craft, RM., Muenchen, RA., Carroll, RC. :|
|Giant platelet disorder in the Cavalier King Charles Spaniel. Exp Hematol 32:344-50, 2004. Pubmed reference: 15050744 . DOI: 10.1016/j.exphem.2004.01.008.|
|2002||Pedersen, H.D., Haggstrom, J., Olsen, L.H., Christensen, K., Selin, A., Burmeister, M.L., Larsen, H. :|
|Idiopathic asymptomatic thrombocytopenia in Cavalier King Charles Spaniels is an autosomal recessive trait Journal of Veterinary Internal Medicine 16:169-173, 2002. Pubmed reference: 11899033 .|
|1997||Smedile, L.E., Houston, D.M., Taylor, S.M., Post, K., Searcy, G.P. :|
|Idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles Spaniels - 11 cases (1983-1993) Journal of the American Animal Hospital Association 33:411-415, 1997. Pubmed reference: 9278116 .|
|1994||Eksell, P., Haggstrom, J., Kvart, C., Karlsson, A. :|
|Thrombocytopenia in the Cavalier King Charles Spaniel. Journal of Small Animal Practice 35:153-155, 1994.|
- Created by Imke Tammen2 on 26 Sep 2021
- Changed by Imke Tammen2 on 26 Sep 2021