THE MOLECULAR AND CLINICAL BIOLOGY OF VON WILLEBRAND DISEASE (VWD)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究旨在探讨血管性血友病因子(VWF)或相关基因的遗传缺陷与其临床诊断和治疗的关系。假设大多数VWD是由VWF基因突变引起的，该突变导致VWF减少或异常，从而导致临床出血和VWD的诊断。这些研究人员将研究以前诊断为VWD的家系，并确定出血症状、VWF蛋白异常以及与VWF基因或其他影响VWF水平或出血症状的基因中的分子缺陷的联系。人们认识到，在小鼠系统中，可能存在VWF水平的修饰基因(如ABO血型)和潜在的其他基因，如糖基化酶，它们可以通过改变VWF清除率而导致1型VWD表型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to study the relationship between genetic defects of the von Willebrand factor (VWF) or related genes and the clinical impact on the diagnosis and management of their von Willebrand disease (VWD) bleeding disorder. The hypothesis is that most VWD is caused by a mutation in the VWF gene that causes reduced or abnormal VWF to be produced and this results in clinical bleeding and the diagnosis of VWD. These investigtors will study families in which there is a previous diagnosis of VWD and determine the segregation of bleeding symptoms, VWF protein abnormalities, and linkage with molecular defects in the VWF gene or other genes affecting VWF levels or bleeding symptoms. It is recognized that there may be VWF-level modifying genes (such as ABO blood type) and potential other genes such as glycosylation enzymes that in the murine system can cause the type 1 VWD phenotype by altering rates of VWF clearance.