In other species: horse

Categories: Haematopoietic system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613554 (trait) , 613160 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2004

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.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in other species), Kramer et al. (2004) showed that a likely causal variant for this disorder in German Shorthaired Pointers is a base substitution in exon 28 of the VWF gene (c.4937A>G; p.Asn1646Ser).

Vos-Loohuis et al. (2017) reported that the most likely causal variant for this disorder in a German Wirehaired Pointer is another missense variant c.1657T>G; p.Trp553Gly. They also reported that "Based on the polyphen-2 predictions and the observation that only the c.1657G (p.553Gly) variant is exclusively found in the homozygous state in GWP and GSP dogs that are affected by VWD, we suggest that this mutation is a primary candidate causal mutation for the disease in the breeds."

Prevalence: Vos-Loohuis et al. (2017) reported "that the c.1657G allele fully segregates with the c.4937G allele and VWD in the GSP breed as it does in the GWP breed. . . . that the c.4937G variant but not the c.1657G allele is present in the Chinese Crested dog breed. Of the 41 tested dogs of this breed, 14 were carriers and three were homozygous for the c.4937G allele. Owners of the Chinese Crested dogs that were homozygous for this variant were contacted, and none of the dogs had signs of a bleeding disorder."

Breeds: Chinese Crested Dog, German Shorthaired Pointer, German Wirehaired Pointer.

Associated gene: