Von Willebrand's Disease 1 (VWF gene)

Von Willebrand's disease affects the function of platelets, which are vital blood cells for the clotting process. This pathology is divided into three types depending on the severity of symptoms, with type 1 being the most common and mildest.

Symptoms

Dogs with von Willebrand disease may have symptoms that include easy or prolonged bleeding, such as nosebleeds, bleeding from the gums, or bleeding after surgery or injury. In the most severe cases, the dog may suffer internal bleeding that can be life-threatening.

Disease Management

There is no cure for the disease, but symptoms can be managed with supportive care such as blood transfusions during severe bleeding episodes.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Von Willebrand's disease is the most commonly observed genetic bleeding disorder in dogs and is quite characteristic in Doberman Pinscher dogs. This disease is caused by abnormalities in von Willebrand factor (vWF), a protein crucial for blood clotting. VWF is a large protein that is synthesized in endothelial cells lining blood vessels and in megakaryocytes, the precursor cells of platelets, in the bone marrow. VWF has a dual role in coagulation, it transports another clotting factor in the blood, factor VIII, and participates in the adhesion of platelets to damaged epithelium when there is an injury. Depending on the severity of symptoms and alteration of vWF it is classified into 3 types. Type 1, characterized by low plasma concentrations of vWF and mild to moderate hemorrhagic symptoms. Type 2 is characterized by qualitative abnormalities of vWF protein and moderate to severe bleeding. Type 3 is the most severe form of the disease and the least frequent, in which vWF is virtually undetectable. Here we analyze the c.7437G>A variant of the VWF gene that encodes for VWF protein and has been linked to type 1 von Willebrand disease. It is important to keep in mind that there is great variability in symptomatology between animals. Crespi et al. observed that some, but not all, Doberman Pinscher dogs had symptoms with a single copy of c.7437G>A and therefore, in this breed, the variant could follow an autosomal dominant mode of inheritance with incomplete penetrance. However, other studies suggest that in other breeds von Willebrand's disease type 1 follows an autosomal recessive mode of inheritance, i.e., symptoms develop when two copies of c.7437G>A are present.

Most affected breeds

Corgi
Doberman Pinscher
German Shepherd Dog
Golden Retriever
Kromfohrländer
Miniature Poodle
Pembroke Welsh Corgi
Shetland Sheepdog
Yorkshire Terrier

Bibliography

Crespi JA, Barrientos LS, 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. 2018 Mar;30(2):310-314.

Gentilini F, Turba ME. Two novel real-time PCR methods for genotyping the von Willebrand disease type I mutation in Doberman Pinscher dogs. Vet J. 2013 Aug;197(2):457-60.