Testing of dogs: VWD type I

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Combination American Hairless Terrier PLL + PRA-prcd + vWDI + DM + hairless
Combination Australian Labradoodle CNM + DM* (SOD1A) + NEWS + PRA-prcd + PRA-rcd4 + Dwarfism (Skeletal dysplasia 2) + VWD type I + DMD
Combination Australian Silky Terrier PRA-prcd + PLL + vWD type I
Combination Australian Terrier LOA + PLL + vWD I
Combination Barbet - French Water Dog HUU + PRA-prcd + vWD I + vWD II + locus D1 + locus KB
Combination Basset Hound FVII + vWD I + Thrombopatia
Combination Bernese Mountain Dog DM (SOD1A) + DM (SOD1B) + vWD I
Combination Coton de Tuléar BNAt + CMR2 + DM (SOD1A) + HUU + IVDD + PHI + PRA-prcd + vWDI
Combination Dachshund Miniature Long-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dachshund Miniature Smooth-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dachshund Miniature Wire-haired Mucopolysaccharidosis IIIA + Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dachshund Standard Long-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dachshund Standard Smooth-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dachshund Standard Wire-haired Mucopolysaccharidosis IIIA + Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Dobermann VWD type I + DM* (SOD1A) + Locus B + Locus D (allele D1) + Deafness in Doberman Pinscher
Combination German Shepherd Dog 1 DM (SOD1A) + Dwarfism + FGF5 + HUU + LAD3 + MDR1 + vWDI
Combination Golden Retriever 2 vWDI + Epidermolysis bullosa + Osteogenesis imperfecta + DM + CMS in Golden Retrievers
Combination Irish Red Setter and Irish Red and White Setter CLAD + DM (SOD1A) + PRA-rcd1 + PRA-rcd4 + vWDI
Combination Kerry Blue Terrier CMSD + DM (SOD1A) + vWDI
Combination Kromforländer HFH + HUU + vWDI + DM* (SOD1A) + MDR1
Combination Manchester terrier PLL + PRA-prcd + vWDI + Xanthinuria II in Manchester Terriers
Combination Papillon and Phaléne DM (SOD1A) + FVII + NAD + papPRA1 + PRA-prcd + vWDI
Combination Poodle NEWS + prcd-PRA + rcd4-PRA + DM(SOD1A) + vWD1 + GM2 + loci E and B
Combination Pug DM (SOD1A) + PKdef + PLL + vWDI + MHA
Combination Puli DM (SOD1A) + PLL + PRA-prcd + vWDI + BBS4
Combination Rabbit Dachshund Long-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Rabbit Dachshund Smooth-haired Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Rabbit Dachshund Wire-haired Mucopolysaccharidosis IIIA + Narcolepsy + NCL1 + OI + VWDI + Xanthinuria II in Dachshunds
Combination Rottweiler DM (SOD1A) + JLPP + vWDI + FGF5 + LEMP in Great Danes and Rottweilers + NAD + MTM1 + Deafness in Rottweilers
Combination Schipperke Short Tail + PRA-prcd + vWDI
Combination Schnauzer Miniature CMT + MAC + MC + PMDS+ PRA1 + SCD + vWDI
Combination Welsh Corgi Cardigan IVDD + DM (SOD1A) + wVDI + XSCID + PRA-rcd3 + FGF5
Combination Welsh Corgi Pembroke IVDD + DM (SOD1A) + wVDI + Short Tail - Bob Tail + XSCID + FGF5
Combination West Highland White Terrier CMO + GLD + PLL + vWDI + PK deficiency in WGWT
DM (SOD1A) + vWDI
vWD I + DM (SOD1A)*
vWD I + PRA-prcd for Poodles, Labradoodles, Goldendoodles

von Willebrand disease

Von Willebrand disease (vWD) is caused by plasmatic von Willebrand factor (vWF) insufficiency. VWF is a blood glycoprotein (not enzyme) important for blood coagulability.

Its primary function is to bind itself to other proteins (for example it stabilizes Factor VIII), and also facilitates aggregation and adhesion of the trombocytes to wound site. The deficiency or failure of vWF function causes bleeding which is most apparent in tissues having high blood flow shear in narrow vessels. VWD manifests oneself as a tendency to bleeding from skin and tissues. The disease can be inheritable or acquired.

In dogs (as well as in people), there were identified three types of vWD. Several gene variants associated with von Willebrand's disease have been identified. It is probable, that another variants will be found in the future.

vWD type I

VWD type I is the most often and simultaneously the least serious form of mammalian vWD. It is inherited autosomal recessively. The disease is characteristic by low plasma vWF concentration and normal vWF protein structure.

Affected dogs may suffer from bleeding problems, usually not very serious. vWD type I occurs, for example, in dog breeds:

Bernese mountain dog
Doberman pinscher
Manchester terrier
Kerry blue terrier
Welsh Corgi Pembroke
Poodle
Labradoodle
Goldendoodle
Miniature Schnauzer
Basethound
German Shepherd
Rotttweiler
Keeshound
Dachshund (standard, mini)
Coton de Tulear
Drentsche Patrijschond
Papillion
Stabyhoun

The casual mutation in this breed is c.7437G>A in exon 43 of vWF-gene (NM_001002932.1). The mutation occurs at a splice site where in healthy dogs (genotype c.7437GG) splicing takes place during synthesis of von Willebrand factor. In addition, there is an alternative splice site that is activated if the variant c.7437A is present. Consequently, the von Willebrand factor is also created in the body of an affected individual, however, with a different number of amino acids. The presence of this cryptic vWF prevents prolonged and excessive bleeding.

The mutation is inherited autosomal recessively, which means that the disease occurs only in individuals, who inherit mutation from both biological parents. The individuals with one mutated allele are disease carriers without any clinical symptoms.

In the Doberman pinscher population in the USA there is about 36% vWD affected dogs and about 48% of carriers. The frequency of mutated gene in the whole population is estimated on a level of 60% (Brewer 2006).

References:

Brewer, G: DNA Studies in Doberman von Willebrand's Disease. The Mutation Discovered and a DNA Test Developed.

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