title: Understanding von Willebrand's disease from gene defects to the patients.
abstract: von Willebrand's disease (vWD) is caused by qualitative (type 2) and quantitative (types 1 and 3) abnormalities of von Willebrand factor (vWF). vWD type 3, a severe form of the disease with nearly complete deficiency of the protein in plasma, are found to be homozygous or compound heterozygous for null mutations in the vWF gene. Null mutations in both alleles of the vWF gene completely disrupt the protein synthesis resulting in a nearly complete deficiency of the vWF in the type 3 patients. The vWD type 1 patients (mild form with partial deficiency of the protein) could be heterozygous for null mutations or compound heterozygous for the mutations (null mutation + missense mutation) in the gene. The vWD type 2, divided into four variants: types 2A, 2B, 2M and 2N, are caused exclusively by missense mutations within three different domains of the protein (gain or loss of function). The majority of type 2A mutations are located in the A2 domain and the types 2B and 2M mutations are in the A1 domain, while the type 2N mutation is in the FVIII binding domain.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Blombäck
authors.forename: M
authors.initials: M
authors.lastname: Anvret
mesh_terms: D005838:Genotype; D006801:Humans; D010641:Phenotype; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor