The Paw Print Genetics Blog

The Von Willebrand Disease Type II Mutation and the Boykin Spaniel

The Von Willebrand Disease Type II Mutation and the Boykin Spaniel

Von Willebrand disease (vWD) is a group of relatively common, inherited disorders of blood clotting in dogs. First described in humans in the 1920’s, vWD is now known to be caused by various mutations in the vWF gene which serves as a blueprint for a protein known as von Willebrand factor (vWF). The vWF protein plays an important role in the cessation of bleeding by binding and adhering platelets to wound sites. VWD is categorized into three main classifications (I, II, and III) based upon the quantity and structure of vWF protein present in affected dogs.

In 2004, a scientific paper was published by Kramer and others which described a specific mutation in the canine VWF gene associated with vWD in the German shorthaired pointer (around the same time, the same mutation was also identified as a cause of excessive bleeding in the German wirehaired pointer). Classified by clinical presentation as von Willebrand disease type II (vWDII), the discovered vWDII mutation has only been described in the scientific literature for the two German pointer breeds. However, the Paw Print Genetics laboratory identified the same mutation in several other breeds including the Boykin Spaniel. To our surprise, the mutation has been found in a relatively high frequency in the breed causing alarm among Boykin breeders. However, at this time the clinical ramifications of this mutation in Boykins are unknown. The goal of this blog is to describe the current state of our knowledge about vWDII in the Boykin spaniel and to discuss additional testing options that may help the Boykin community better understand the clinical significance of this mutation’s presence in the breed.

Genetic testing for vWDII

Paw Print Genetics provides genetic testing for a variety of disease mutations found in the canine genome. Among these, is the mutation found in the vWF gene, which has been correlated with abnormal bleeding in some breeds, characterized as vWDII. The methods used at Paw Print Genetics are highly reliable. In addition, because we test the mutation region twice, with two independent methods and the results of these two independent methods must agree before reporting, our DNA-based test is highly accurate for identifying the mutation. Thus, the DNA-based test is very effective in identifying the mutation. What remains to be understood is the correlation between carrying two copies of this mutation and the clinical presentation of a bleeding disorder.  

Does the vWDII mutation have clinical significance for Boykin spaniels?

In both dogs and humans with vWD, significant variability exists in the clinical presentation between “genetically affected” individuals with the same mutation. Though we have heard anecdotal reports at Paw Print Genetics about Boykin spaniels developing severe bleeding episodes leading to death after surgery and giving birth, the dog owners which informed us about their experience did not have any additional diagnostic lab work performed at the time to determine if the vWDII-associated mutation was the potential cause of the bleeding. However, given the clinical signs seen in vWDII affected German pointers, a clinical investigation into this condition in Boykins is warranted. That being said, the presence of the vWDII mutation alone is not enough to prove causation in terms of the clotting abnormalities identified clinically. It is for this reason that we are recommending that owners of any Boykin spaniel found to have inherited two copies of the vWDII-associated mutation to also consider having two additional vWF protein-based tests performed:

1.von Willebrand factor Antigen test- Determines the concentration of vWF protein present in the dog’s blood.

2.von Willebrand factor collagen binding assay- Determines the activity/function of the vWF protein that is present in the dog’s blood.

1. Von Willebrand Factor Antigen Testing

Historically, one of the most common methods of identifying vWD affected dogs is the blood test referred to as the vWF antigen assay. This assay tests for the concentration of vWF protein in a dog which is then compared to a control value for normal dogs. Dogs fall into either normal, borderline, or abnormal categories based upon this ratio. In normal dogs, small vWF protein subunits bind together to form larger protein structures known as multimers. These large multimers are the most effective of the vWF units contributing to the cessation of bleeding. In dogs affected with vWDII, vWF is still produced, but there is a significant decrease in the presence of these large multimers, thereby decreasing the ability of the dog to clot normally. In most cases of affected German pointers, this assay shows a low overall concentration of vWF protein. This assay does not differentiate between small, relatively ineffective vWF subunits and the large vWF multimers that play the primary role in clotting.

2. Von Willebrand Factor Collagen Binding Assay

Though the vWF antigen assay can be very useful in determining the concentration of vWF in the blood (a quantitative test), it is unable to give us information about the actual activity or function of the vWF (a qualitative parameter) in the dog. Qualitative information about the clotting ability of a suspected vWDII-affected dog can be obtained by performing a test known as the von Willebrand factor collagen binding assay. In some cases, the collagen binding assay can yield more clinically relevant information about how the factor is actually functioning in the dog and, thus, may provide more information about potential bleeding problems than the antigen assay alone.

Reporting Results to Paw Print Genetics

Paw Print Genetics is committed to providing reliable and accurate genetic testing to the dog breeding community. In order for our clients to obtain a better understanding of the potential vWDII-associated bleeding risks in the Boykin spaniel, we are recommending owners of Boykins which have inherited two copies of the vWDII-associated mutation to strongly consider ordering the two protein-based assays discussed above from Cornell University’s Animal Health Diagnostic Center. In addition, we are kindly asking that these clients then submit the Cornell test results to our laboratory for correlation with our DNA-based results. It is our assumption that this information will prove invaluable in determining the risks associated with the vWDII-associated mutation in the Boykin spaniel. It should be noted that Cornell University has been recommended due to the high quality and significant experience of this laboratory in von Willebrand testing and research. Paw Print Genetics has no association with Cornell and does not receive any incentive (financial or otherwise) to recommend this laboratory.

If you have questions about vWDII in the Boykin spaniel or have other general canine genetic health questions, please feel free to contact Paw Print Genetics at AskUs@pawprintgenetics.com or chat with one of our laboratory directors by calling the Paw Print Genetics laboratory (509-483-5950) during our regular business hours (Mon. through Fri., 8 am to 5 pm PST).

*Photo courtesy of MIchael Shaffer via Flickr Creative Commons license*