OMIA:001058-9615 : Von Willebrand disease III in Canis lupus familiaris
In other species: domestic cat , pig
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 277480 (trait) , 613160 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 1998
Cross-species summary: The von Willebrand factor (vWF) is a large multimeric plasma glycoprotein required for platelet adhesion and aggregation. A deficiency or defective vWF results in von Willebrand disease (vWD). vWD are often classified in 3 different types based on the clinical severity and quantity and multimere size of von Willebrand factor. Type I is characterized by low plasma vWF concentrations and mild to moderate bleeding symptoms. Type II disorder is characterised by qualitative abnormalities of the vWF protein and moderate to severe bleeding. Type III is the most severe form of vWD with no detectable or a severe quantitative deficiency of vWF.
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Rieger et al. (1998) showed the molecular basis for this disorder in Dutch Kooiker dogs to be a frameshift mutation in the gene encoding von Willebrand factor. Specifically, a G>A base substition at the first position of the donor splice site sequence of intron 16 results in a transcript containing 46 bases of intron, and creates a stop codon at amino acid position 729.
Venta et al. (2000) reported "a single base deletion in the codon for amino acid 85 of the prepro-vWF cDNA" as a causal mutation in Scottish Terriers.
As reported by Boudreaux (2012), a causal mutation in the Shetland Sheepdog breed was reported in US Patent 6074832 by Brewer et al. (Michigan State University) in 2000. To FN's knowledge, this discovery has not been published in the peer-reviewed literature. If anyone knows of a relevant publication, please contact FN.
Breeds: Dutch Kooiker, Scottish Terrier, Shetland Sheepdog.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|VWF||von Willebrand factor||Canis lupus familiaris||27||NC_051831.1 (39191850..39329540)||VWF||Homologene, Ensembl , NCBI gene|
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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|
|479||Scottish Terrier||Von Willebrand disease III||VWF||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||27||g.38848107del||c.255del||p.(V86Cfs)||NM_001002932.1; NP_001002932.1; "a single base deletion [C] in the codon for amino acid 85 of the prepro-vWF cDNA"||2000||10668811|
|968||Shetland Sheepdog||Von Willebrand disease III||VWF||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||27||g.38868884del||c.738del||p.(F366Lfs)||NM_001002932.1; NP_001002932.1; Venta, P. J., G. J. Brewer, V. Yuzbasiyan-Gurkan, W. D. Schall, and J. Duffendeck, 1998 Inventors; The Regents of the University of Michigan, assignee. DNA encoding canine von Willebrand factor and methods of use. United States patent US6074832A. 1998 Aug 11.||1998||Reference not in PubMed; see OMIA 001058-9615 for reference details|
|371||Dutch Kooiker||Von Willebrand disease III||VWF||splicing||Naturally occurring variant||CanFam3.1||27||g.38892182G>A||c.2186+1G>A||NM_001002932.1; a G>A base substitution at the first position of the donor splice site sequence of intron 16||1998||9716162|
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.
|2021||Arruda, V.R., Weber, J., Samelson-Jones, B.J. :|
|Gene therapy for inherited bleeding disorders. Semin Thromb Hemost 47:161-173, 2021. Pubmed reference: 33636747 . DOI: 10.1055/s-0041-1722862.|
|2016||Nichols, T.C., Hough, C., Agersø, H., Ezban, M., Lillicrap, D. :|
|Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies. J Thromb Haemost 14:894-905, 2016. Pubmed reference: 26924758 . DOI: 10.1111/jth.13301.|
|2012||Boudreaux, M.K. :|
|Inherited platelet disorders. J Vet Emerg Crit Care (San Antonio) 22:30-41, 2012. Pubmed reference: 22316339 . DOI: 10.1111/j.1476-4431.2011.00702.x.|
|2009||Burgess, H.J., Woods, J.P., Abrams-Ogg, A.C., Wood, R.D. :|
|Evaluation of laboratory methods to improve characterization of dogs with von Willebrand disease. Can J Vet Res 73:252-259, 2009. Pubmed reference: 20046626 .|
|2004||Pathak, EJ. :|
|Type 3 von Willebrand's disease in a Shetland sheepdog. Can Vet J 45:685-7, 2004. Pubmed reference: 15368744 .|
|van Oost, BA., Versteeg, SA., Slappendel, RJ. :|
|DNA testing for type III von Willebrand disease in Dutch Kooiker dogs. J Vet Intern Med 18:282-8, 2004. Pubmed reference: 15188812 .|
|2000||Venta, P.J., Li, J.P., Yuzbasiyan-Gurkan, V., Brewer, G.J., Schall, W.D. :|
|Mutation causing von Willebrand's disease in Scottish terriers Journal of Veterinary Internal Medicine 14:10-19, 2000. Pubmed reference: 10668811 .|
|1999||Denis, C.V., Wagner, D.D. :|
|Insights from von Willebrand disease animal models. Cell Mol Life Sci 56:977-90, 1999. Pubmed reference: 11212329 . DOI: 10.1007/s000180050487.|
|Johnstone, I.B. :|
|Plasma von Willebrand factor-collagen binding activity in normal dogs and in dogs with von Willebrand's disease Journal of Veterinary Diagnostic Investigation 11:308-313, 1999. Pubmed reference: 10424644 .|
|1998||Rieger, M., Schwarz, H.P., Turecek, P.L., Dorner, F., Vanmourik, J.A., Mannhalter, C. :|
|Identification of mutations in the canine von Willebrand factor gene associated with type III von-Willebrand-disease Thrombosis and Haemostasis 80:332-337, 1998. Pubmed reference: 9716162 .|
|Slappendel, R.J., Beijer, E.G.M., Vanleeuwen, M. :|
|Type III von-Willebrands-disease in Dutch Kooiker dogs Veterinary Quarterly 20:93-97, 1998. Pubmed reference: 9684296 .|
|Stokol, T., Parry, B.W. :|
|Efficacy of fresh-frozen plasma and cryoprecipitate in dogs with Von-Willebrands-disease or hemophilia a Journal of Veterinary Internal Medicine 12:84-92, 1998. Pubmed reference: 9560764 .|
|Venta, P.J., Brewer, G.J., Yuzbasiyan-Gurkan, V., Schall, W.D., Duffendeck, J. :|
|Inventors; The Regents of the University of Michigan, assignee. DNA encoding canine von Willebrand factor and methods of use. United States patent US6074832A. 1998 Aug 11 :, 1998.|
|1996||Thomas, J.S. :|
|von Willebrand's disease in the dog and cat. Vet Clin North Am Small Anim Pract 26:1089-110, 1996. Pubmed reference: 8863392 .|
|1993||Brooks, M., Catalfamo, J. :|
|Buccal mucosa bleeding time is prolonged in canine models of primary hemostatic disorders. Thrombosis and Haemostasis 70:777-780, 1993. Pubmed reference: 8128434 .|
|Johnstone, I.B., Norris, A.M., Hirzer, L. :|
|Type-III von Willebrand's Disease in Scottish Terriers - A Report of 2 Cases Canadian Veterinary Journal - Revue Veterinaire Canadienne 34:679-681, 1993.|
|1988||Johnson, G.S., Turrentine, M.A., Kraus, K.H. :|
|Canine von Willebrand's disease. A heterogeneous group of bleeding disorders. Vet Clin North Am Small Anim Pract 18:195-229, 1988. Pubmed reference: 3282380 . DOI: 10.1016/s0195-5616(88)50017-7.|
- Created by Frank Nicholas on 12 Sep 2005
- Changed by Frank Nicholas on 29 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 04 Sep 2012
- Changed by Frank Nicholas on 23 Apr 2013