In other species: domestic cat , pig

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 277480 (trait) , 613160 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Disease-related: yes

Key variant known: yes

Year key variant first reported: 1998

Cross-species summary: The von Willebrand factor (vWF) is a large multimeric plasma glycoprotein required for platelet adhesion and aggregation. A deficiency or defective vWF results in von Willebrand disease (vWD). vWD are often classified in 3 different types based on the clinical severity and quantity and multimere size of von Willebrand factor. Type I is characterized by low plasma vWF concentrations and mild to moderate bleeding symptoms. Type II disorder is characterised by qualitative abnormalities of the vWF protein and moderate to severe bleeding. Type III is the most severe form of vWD with no detectable or a severe quantitative deficiency of vWF.

Inheritance: Venta et al. (2000) report that type 3 con Willebrand's disease is inherited as an autosomal recessive trait in dogs. 

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Rieger et al. (1998) showed the molecular basis for this disorder in Dutch Kooiker dogs to be a frameshift mutation in the gene encoding von Willebrand factor. Specifically, a G>A base substition at the first position of the donor splice site sequence of intron 16 results in a transcript containing 46 bases of intron, and creates a stop codon at amino acid position 729. Venta et al. (2000) reported "a single base deletion in the codon for amino acid 85 of the prepro-vWF cDNA" as a causal mutation in Scottish Terriers. As reported by Boudreaux (2012), a causal mutation in the Shetland Sheepdog breed was reported in US Patent 6074832 by Brewer et al. (Michigan State University) in 2000. To FN's knowledge, this discovery has not been published in the peer-reviewed literature. If anyone knows of a relevant publication, please contact FN.

Breeds: Nederlandse Kooikerhondje (Dog) (VBO_0200932), Scottish Terrier (Dog) (VBO_0201198), Shetland Sheepdog (Dog) (VBO_0201217).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: