The molecular basis of von Willebrand disease

von Willebrand disease (VWD) is a clinically heterogeneous bleeding disorde r that reflects a wide array of defects. Quantitative subtypes of the disor der, including types 1 and 3 VWD, result in bleeding due to reduced levels of circulating von Willebrand factor (VWF) protein. Qualitative subtypes, d efined as type 2 VWD, act through altered VWF function. A range of molecula r defects are responsible for many of these subtypes, including missense, n onsense, splicing, insertion, and deletion mutations, resulting in either d ominant or recessive inheritance. While many mutations correspond to select ed variants, the basis for variation in expression and the imperfect correl ations between genotype and phenotype remain to be understood.