Von Willebrand Disease, type 2 (vWD 2)

 

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.

Mutations:

German Shorthaired Pointer mutation: Substitution, VWF gene; c.4937 A>G, p.(N1646S), exon28

Chinese Crested mutation: Substitution, VWF gene; c.1657 T>G, p.(W553G)

Medical system: Blood

Breeds: Barbet, Boykin Spaniel, Chinese Crested, Collie, German Shorthaired Pointer, German Spitz, German Wirehaired Pointer

Age of onset of symptoms: First weeks of life or after the first veterinary surgery

The Von Willebrand factor (vWF) is a protein required for normal blood coagulation after injury or after surgery.  Type 2 Von Willebrand disease is a bleeding disorder that results when the vWF protein is defective due to a genetic mutation.  Affected dogs may bruise easily, have frequent nosebleeds and can have excessive bleeding due to the loss of baby teeth.  Clinical signs can be moderate to severe.  Trauma and surgeries are problematic as affected animals can die due to uncontrolled bleeding if transfusions are not made available.  On the other hand, affected animals kept under normal conditions can have a normal lifespan.

Note the different clinical presentations of von Willebrand Disease, caused by different mutations in the VWF gene:

vWD1     (mild to moderate clinical symptoms)

vWD2     (moderate to severe clinical symptoms)

vWB3     (severe clinical symptoms)

 

References:

OMIA link: [1339-9615]

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]

Vos-Loohuis M, van Oost BA, Dangel C, Langbein-Detsch I, Leegwater PA. (2017) A Novel VWF Variant Associated With Type 2 Von Willebrand Disease in German Wirehaired Pointers and German Shorthaired Pointers. Anim Genet. 48(4):493-496. [pubmed/28696025]

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

Gavazza A, Presciuttini S, Keuper H et al. (2012) Estimated prevalence of canine Type 2 Von Willebrand disease in the Deutsch-Drahthaar (German Wirehaired Pointer) in Europe. Res Vet Sci. 93(3):1462-6. [pubmed/22824509]

Kramer JW, Venta PJ, Klein SR et al. (2004) 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(3):221-8. [pubmed/15133170]

van Dongen AM, van Leeuwen M, Slappendel RJ. (2001) Canine von Willebrand’s disease type 2 in German wirehair pointers in the Netherlands. Vet Rec. 148(3):80-2. [pubmed/12503596]