Von Willebrand Disease, type3 (vWD 3)

 

Gene: VWF

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation:

Kooikerhondje type: Substitution, VWF gene; c.2186+1 G>A

Shetland Sheepdog type: Délétion, VWF gene; c.738 del. T, p.(F366 L, fs)

Scottish Terrier type: Délétion, VWF gene; c.255 del, p.(V86C, fs)

Breeds: Chihuahua, Kooikerhondje, Scottish Terrier, Shetland Sheepdog

Age of onset of symptoms: From birth, after a trauma or surgery.

Von Willebrand factor (VWF) is a blood glycoprotein that  is essential for coagulation, the biological process that stops bleeding after injury or surgery. Von Willebrand disease type 3 (vWB3) is a severe bleeding disorder that occurs when the VWF protein is completely absent due to a specific mutation in the VWF gene. Clinical signs include excessive bruising, mucous membrane bleeding (especially gum bleeding), bloody diarrhoea, vomiting of blood, blood in the urine, nosebleeds, prolonged oestrus and excessive bleeding from small wounds and veterinary procedures such as excision of deciduous (milk) teeth or other surgeries. Clinical signs can be severe, with potentially fatal external and internal bleeding. Trauma and surgery are thus problematic, as affected animals can die from uncontrolled bleeding if transfusions are not available. Several independent mutations in the VWF gene have occurred that are responsible for vWB3 disease in several breeds of dog; appropriate DNA tests are available for the breed in question.

 

References:

OMIA link: [1058-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Haginoya S, Thomovsky EJ, Johnson PA, Brooks AC. (2023) Clinical assessment of primary hemostasis: A review. Top Companion Anim Med :100818.  [pubmed/37673175]

Nichols TC, Hough C, Agersø H, Ezban M, Lillicrap D. (2016) Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies. J Thromb Haemost 14:894-905. [pubmed/26924758]

Scuderi M, Bessey L, Snead E, Burgess H, Carr A. (2015) Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog. Can Vet J. 56(9):937-41. [pubmed/26347307]

Boudreaux MK. (2012) Inherited platelet disorders. J Vet Emerg Crit Care (San Antonio) 22:30-41. [pubmed/22316339]

Pathak EJ. (2004) Type 3 von Willebrand’s disease in a Shetland sheepdog. Can Vet J 45:685-7. [pubmed/15368744]

van Oost BA, Versteeg SA, Slappendel RJ. (2004) DNA testing for type III von Willebrand disease in Dutch Kooiker dogs. J Vet Intern Med 18:282-8. [pubmed/15188812]

Venta PJ, Li J, Yuzbasiyan-Gurkan V et al. (2000) Mutation causing von Willebrand’s disease in Scottish Terriers. J Vet Intern Med. 14(1):10-9. [pubmed/10668811]

Rieger M, Schwarz HP, Turecek PL, et al. (1998) Identification of mutations in the canine von
Willebrand factor gene associated with type III von Willebrand disease. Thromb Haemost. 80(2):332-77. [pubmed/9716162]

Raymond SL, Jones DW, Brooks MB, Dodds WJ. (1990) Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs. J Am Vet Med Assoc. 197(10):1342-6. [pubmed/2266049]

 

Contributed by: Émilie Gagnon and Samy Chami-Tondreau, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).