vWDI is inherited in an autosomal dominant manner with incomplete penetrance, in the Kromfohrländer breed

Abstract

Background Von Willebrand disorder type I (vWDI) is known as an inherited bleeding disorder in different dog breeds following an autosomal recessive inheritance. The Kromfohrländer is a rare dog breed with an increased incidence of unclear bleeding episodes and prolonged coagulation time during/after surgery or injuries, indicating a defect in one or more critical proteins of the coagulation cascade. Objective The objective of this study was to determine whether the c.7437G > A mutation in the VWF gene previously shown to cause von Willebrand disorder type I in Doberman Pinscher is also linked to this disease in the Kromfohrländer breed and to serum concentrations of vWF. Furthermore, establish a possible link between bleeding phenotype, vWF serum concentrations and VWF mutation status. Results Eighty-seven Kromfohrländer were genotyped for the G > A von Willebrand type I mutation. For detection of the associated mutation we used an endpoint genotyping method. We identified the G > A von Willebrand type I mutation in 80.5% of our study population. 65.5% were heterozygous (WT/MUT) and 15.0% were homozygous for the mutation (MUT/MUT). 21% of the overall study population exhibited bleeding symptoms. 45.5% of all homozygous dogs (MUT/MUT) showed bleeding symptoms. In contrast, wild-type homozygotes exhibited no bleeding symptoms, whereas 23.2% of the heterozygotes did. 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) Conclusion Based on our data, we found the G > A mutation in the VWF gene in the Kromfohrländer breed and the subsequent vWDI as the underlying cause for the bleeding episodes and delayed coagulation in heterozygous and homozygous dogs. Since both, heterozygotes and homozygotes show reduced vWF serum concentrations and exhibit to a certain percentage the vWD syndrome phenotype, we postulate that, in contrast to most other vWDI affected breeds, inheritance follows an autosomal dominant mode with incomplete penetrance.

Case report of unilateral retrobulbar hematoma associated with von Willebrand disease in a Doberman Pinscher dog

“…The defect has been reported in more than 70 breeds and affects more than half of the Doberman Pinschers population 13 . Inheritance of the disease is described in most breeds as an autosomal recessive trait 14 . vWD should be suspected in any dog showing a combination of bleeding tendencies manifested by a prolonged BMBT, especially after surgery or trauma and that has a normal platelet counts, PT, and aPTT 1 .…”

“…Administration of DDAVP, a synthetic analogue of the neurohypophyseal hormone arginine vasopressin, can temporarily increase the vWF plasma concentration. Despite this modest increase in plasma vWF concentration, administration of DDAVP to Doberman Pinschers with type 1 vWD only results in a transient improvement of hemostatic function 14 . Cryoprecipitate or fresh‐frozen plasma should be used intraoperatively if significant bleeding occurs during surgery of dogs with vWD 1…”

Investigation of a common canine factor VII deficiency variant in dogs with unexplained bleeding on autopsy

“…VWD is separated into types associated with several variants (at least one of which may not be causal) and is found in dozens of dog breeds. 2,5,10,12,13,23,24,36,37,42,43 None of the case cohort samples were tested for any of the VWD variants; however, several of the breeds represented in our cases are documented to carry VWD variants, including the Doberman Pinscher, Chinese Crested, Great Dane, and others. Given that VWD variants are also common in mixed-breed and purebred dogs, 13 testing our case population for appropriate VWD variants is a logical next step for future work.…”

Petechien, Hämatome, Epistaxis – Was nun? Ein diagnostischer Leitfaden

“…Dieses ist die häufigste vererbbare Koagulopathie des Hundes. Es wird i. d. R. autosomal dominant, aber mit unvollständiger Penetranz vererbt 3 , 19 , 20 . Obwohl es sich bei dem vWS um eine primäre Koagulopathie handelt, werden klinisch keine Petechien beobachtet.…”