OMIA 001058-9615 : Von Willebrand disease III in Canis lupus familiaris

In other species: domestic cat , pig

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 277480 (trait) , 613160 (gene)

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.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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

References


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.

Edit History


  • 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