von Willebrand disease.
Considerable progress has been made in characterizing the specific molecular defects responsible for the heterogeneous disorder known as von Willebrand disease (VWD). A large number of molecular defects have been identified and precise characterization may now be possible in the majority of type 2A, type 2B, type 2N, and potentially also type 3 VWD cases. However, the most common variant, type 1 VWD, still remains a major challenge. Continued progress in this area will improve our understanding of the pathogenesis of VWD and lead to more rapid and precise diagnosis and classification for this common disorder. The problems of incomplete VWD penetrance and poor diagnostic sensitivity and accuracy for the currently available clinical laboratory tests provide strong incentives for the development of DNA-based diagnostics. In addition, prenatal diagnosis is now possible either at the level of single point mutations (for some subtypes) or by RFLP analysis (assuming linkage to the von Willebrand factor [VWF] gene) and will probably be applied with increasing frequency for VWD type 3 (17, 133, 175). Understanding the molecular basis of VWD also has important implications for VWF structure and function and is helping to define critical binding domains within the VWF molecule. Insights gained from these studies may eventually lead to improved therapeutic approaches not only for VWD, but also for a variety of other genetic and acquired hemorrhagic and thrombotic disorders.
Nichols
W C
WC
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
Ginsburg
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D015342:DNA Probes; D006470:Hemorrhage / Q000628:therapy; D006801:Humans; D008967:Molecular Biology; D017354:Point Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011296:Prenatal Diagnosis; D013927:Thrombosis / Q000628:therapy; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D014841:von Willebrand Factor / Q000235:genetics
D015342:DNA Probes; D014841:von Willebrand Factor