UNDERSTANDING VON-WILLEBRANDS-DISEASE FROM GENE DEFECTS TO THE PATIENTS

von Willebrand's disease (vWD) is caused by qualitative (type 2) and q uantitative (types 1 and 3) abnormalities of von Willebrand factor (VW F). vWD type 3, a severe form of the disease with nearly complete defi ciency of the protein in plasma, are found to be homozygous or compoun d heterozygous for null mutations in the vWF gene. Null mutations in b oth alleles of the VWF gene completely disrupt the protein synthesis r esulting in a nearly complete deficiency of the VWF in the type 3 pati ents. The vWD type 1 patients (mild form with partial deficiency of th e protein) could be heterozygous for null mutations or compound hetero zygous for the mutations (null mutation + missense mutation) in the ge ne. The vWD type 2, divided into four variants: types 2A, 2B, 2M and 2 N, are caused exclusively by missense mutations within three different domains of the protein (gain or loss of function). The majority of ty pe 2A mutations are located in the A2 domain and the types 2B and 2M m utations are in the Al domain, while the type 2N mutation is in the FV III binding domain.