OMIA 001057-9615 : Von Willebrand disease I in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 193400

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1998

Molecular basis: As reported by Boudreaux (2012), a likely causal mutation for this disorder in Doberman Pinchers was reported in US Patent 6074832, submitted by Brewer et al. (Michigan State University) in 2000. According to the patent, the actual mutation is a synonymous base substitution at nucleotide 7437 in exon 43 (Ser 2479) of the VWF gene, which decreases the effectiveness of a splice site. Gentilini and Turba (2013) provided details of the mutation: it is "a G → A transversion of the last nucleotide of von Willebrand factor (vWf) exon 43 (c.7437G > A, NM_001002932.1) . . . [which] activates a cryptic splice site a few nucleotides upstream of the normal splice site, leading to a frame shift that results in the formation of a truncated protein of 119 amino acids".

Crespi et al. (2018) reported that the c.7437A variant is only partially associated with the disorder in the Doberman Pinscher breed in Argentina: only 40% of homozygotes and 22% of heterozygotes for the variant showed clinical signs.

Segert et al. (2019) reported similar results for the Kromfohrländer breed: only 46% of homozygotes and 23% of heterozygotes for the c.7437A variant showed clinical signs. Segert et al. (2019) also reported that the variant locus shows a significant effect on vWF concentration: "VWF serum concentrations varied from 28 to 137% in wild-type dogs while in heterozygous and homozygous dogs the concentration ranged from 3 to 77% and 1 to 23%, respectively (p < 0.05)".

Breeds: Doberman Pincher, Kromfohrländer.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
VWF von Willebrand factor Canis lupus familiaris 27 NC_006609.3 (38834812..38972614) 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Doberman Pinscher Kromfohrländer Von Willebrand disease I VWF splicing CanFam3.1 27 g.38951839G>A c.7437G>A p.Ser2479Ser 2013 23911791 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.
2019 Segert, J.H., Seidel, J.M., Wurzer, W.J., Geretschlaeger, A.M. :
vWDI is inherited in an autosomal dominant manner with incomplete penetrance, in the Kromfohrländer breed. Canine Genet Epidemiol 6:3, 2019. Pubmed reference: 31131110. DOI: 10.1186/s40575-019-0073-4.
2018 Crespi, J.A., Barrientos, L.S., Giovambattista, G. :
von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina. J Vet Diagn Invest 30:310-314, 2018. Pubmed reference: 29271313. DOI: 10.1177/1040638717750429.
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.
2013 Gentilini, F., Turba, M.E. :
Two novel real-time PCR methods for genotyping the von Willebrand disease type I mutation in Doberman Pinscher dogs. Vet J 197:457-60, 2013. Pubmed reference: 23911791. DOI: 10.1016/j.tvjl.2013.02.023.
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.
2005 Callan, MB., Giger, U., Catalfamo, JL. :
Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease. Am J Vet Res 66:861-7, 2005. Pubmed reference: 15938072.
2004 Anonymous :
Detection of von Willebrand disease (vWD) in Doberman, Manchester Terrier and Poodle Kleintierpraxis 49:717-718, 2004.
2002 Callan, M.B., Giger, U. :
Effect of desmopressin acetate administration on primary hemostasis in Doberman Pinschers with type-1 von Willebrand disease as assessed by a point-of-care instrument American Journal of Veterinary Research 63:1700-1706, 2002. Pubmed reference: 12492285.
2001 Brooks, M.B., Erb, H.N., Foureman, P.A., Ray, K. :
von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers American Journal of Veterinary Research 62:364-369, 2001. Pubmed reference: 11277201.
2000 Lutze, G., Kutschmann, K., Aumann, V., Hartung, K.J., Mittler, U. :
Combined von Willebrand disease and factor XII deficiency (vWD San Diego) in the dog and humans [German] Praktische Tierarzt 81:912-+, 2000.
Riehl, J., Okura, M., Mignot, E., Nishino, S. :
Inheritance of von Willebrand's disease in a colony of Doberman Pinschers American Journal of Veterinary Research 61:115-120, 2000. Pubmed reference: 10685679.
1999 Johnstone, I.B. :
Desmopressin enhances the binding of plasma von Willebrand factor to collagen in plasmas from normal dogs and dogs with Type I von Willebrand's disease Canadian Veterinary Journal - Revue Veterinaire Canadienne 40:645-648, 1999.
1998 Brewer, G.J., Venta, P.J., Schall, W., Yuzbasiyan-Gurkan, V., Li, J. :
DNA tests for von Willebrand’s disease in Dobermans, Scotties, Shelties and Manchester terriers. Canine Practice 23:45, 1998.
Moser, J., Meyers, K.M., Russon, R.H., Reeves, J.J. :
Plasma von-Willebrand-factor changes during various reproductive cycle stages in mixed-breed dogs with normal von-Willebrand-factor and in Doberman Pinschers with type-I von-Willebrands-disease American Journal of Veterinary Research 59:111-118, 1998. Pubmed reference: 9442254.
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.
1996 Moser, J., Meyers, K.M., Russon, R.H. :
Inheritance of von Willebrand factor deficiency in Doberman pinschers. J Am Vet Med Assoc 209:1103-6, 1996. Pubmed reference: 8800256.
1995 Meinkoth, J.H., Meyers, K.M. :
Measurement of von Willebrand factor-specific mRNA and release and storage of von Willebrand factor from endothelial cells of dogs with type-I von Willebrands disease American Journal of Veterinary Research 56:1577-1585, 1995. Pubmed reference: 8599517.
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.

Edit History


  • Created by Frank Nicholas on 14 Jul 2006
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 15 Aug 2012
  • Changed by Frank Nicholas on 23 Apr 2013
  • Changed by Frank Nicholas on 29 Aug 2013
  • Changed by Frank Nicholas on 28 May 2019
  • Changed by Frank Nicholas on 01 Aug 2019