Zhang Z, Blombäck M, Anvret M
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Intern Med Suppl. 1997;740:115-9.
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.
血管性血友病（vWD）是由血管性血友病因子（vWF）的质量异常（2型）和数量异常（1型和3型）引起的。3型vWD是该疾病的一种严重形式，血浆中该蛋白几乎完全缺乏，被发现vWF基因的无效突变呈纯合子或复合杂合子状态。vWF基因两个等位基因的无效突变完全破坏了蛋白质合成，导致3型患者的vWF几乎完全缺乏。1型vWD患者（症状较轻，蛋白部分缺乏）可能是该基因无效突变的杂合子，或该基因突变（无效突变+错义突变）的复合杂合子。2型vWD分为四个变体：2A型、2B型、2M型和2N型，完全由该蛋白三个不同结构域内的错义突变（功能获得或丧失）引起。大多数2A型突变位于A2结构域，2B型和2M型突变位于A1结构域，而2N型突变位于FVIII结合结构域。
