OMIA 001339-9615 : Von Willebrand disease II in Canis lupus familiaris

In other species: horse

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613554 (trait) , 613160 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2004

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 disorder in other species), Kramer et al. (2004) showed that a likely causal variant for this disorder in German Shorthaired Pointers is a base substitution in exon 28 of the VWF gene (c.4937A>G; p.Asn1646Ser).

Vos-Loohuis et al. (2017) reported that the most likely causal variant for this disorder in a German Wirehaired Pointer is another missense variant c.1657T>G; p.Trp553Gly. They also reported that "Based on the polyphen-2 predictions and the observation that only the c.1657G (p.553Gly) variant is exclusively found in the homozygous state in GWP and GSP dogs that are affected by VWD, we suggest that this mutation is a primary candidate causal mutation for the disease in the breeds."

Prevalence: Vos-Loohuis et al. (2017) reported "that the c.1657G allele fully segregates with the c.4937G allele and VWD in the GSP breed as it does in the GWP breed. . . . that the c.4937G variant but not the c.1657G allele is present in the Chinese Crested dog breed. Of the 41 tested dogs of this breed, 14 were carriers and three were homozygous for the c.4937G allele. Owners of the Chinese Crested dogs that were homozygous for this variant were contacted, and none of the dogs had signs of a bleeding disorder."

Breeds: Chinese Crested Dog, German Shorthaired Pointer, German Wirehaired Pointer.

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
803 Chinese Crested Dog German Shorthaired Pointer German Wirehaired Pointer Von Willebrand disease II VWF missense Naturally occurring variant CanFam3.1 27 g.38887211T>G c.1657T>G p.(W553G) 2017 28696025 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
84 German Shorthaired Pointer German Wirehaired Pointer Von Willebrand disease II VWF missense Naturally occurring variant CanFam3.1 27 g.38924099A>G c.4937A>G p.(N1646S) rs852456570 rs852456570 2004 15133170 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2017 Vos-Loohuis, M., van Oost, B.A., Dangel, C., Langbein-Detsch, I., Leegwater, P.A. :
A novel VWF variant associated with type 2 von Willebrand disease in German Wirehaired Pointers and German Shorthaired Pointers. Anim Genet 48:493-496, 2017. Pubmed reference: 28696025. DOI: 10.1111/age.12544.
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 Gavazza, A., Presciuttini, S., Keuper, H., Lubas, G. :
Estimated prevalence of canine Type 2 Von Willebrand disease in the Deutsch-Drahthaar (German Wirehaired Pointer) in Europe. Res Vet Sci 93:1462-6, 2012. Pubmed reference: 22824509. DOI: 10.1016/j.rvsc.2012.06.010.
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.
2006 Sabino, E.P., Erb, H.N., Catalfamo, J.L. :
Development of a collagen-binding activity assay as a screening test for type II von Willebrand disease in dogs. Am J Vet Res 67:242-9, 2006. Pubmed reference: 16454628. DOI: 10.2460/ajvr.67.2.242.
2004 Kramer, JW., Venta, PJ., Klein, SR., Cao, Y., Schall, WD., Yuzbasiyan-Gurkan, V. :
A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs. Vet Pathol 41:221-8, 2004. Pubmed reference: 15133170. DOI: 10.1354/vp.41-3-221.
2001 van Dongen, A.M., van Leeuwen, M., Slappendel, R.J. :
Canine von Willebrand's disease type 2 in German wirehair pointers in the Netherlands Veterinary Record 148:80-82, 2001. Pubmed reference: 12503596.
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.
1996 Brooks, M., Raymond, S., Catalfamo, J. :
Severe, recessive von Willebrand's disease in German Wirehaired Pointers. J Am Vet Med Assoc 209:926-9, 1996. Pubmed reference: 8790542.
Brooks, M., Raymond, S., Catalfamo, J. :
Plasma von Willebrand factor antigen concentration as a predictor of von Willebrand's disease status in German Wirehaired Pointers. J Am Vet Med Assoc 209:930-3, 1996. Pubmed reference: 8790543.
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.
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 28 Dec 2010
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 17 Oct 2012
  • Changed by Frank Nicholas on 01 Sep 2017