Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)

作者：Anne C. Goodeve, Jeroen C.J. Eikenboom, Giancarlo Castaman, Francesco Rodeghiero, Augusto Bramante Federici, Javier Batlle, Dominique Meyer, Claudine Mazurier, Jenny Goudemand, Reinhard Schneppenheim, Ulrich Budde, Jørgen Ingerslev, David Habart, Zdena Vorlová, Lars Holmberg, Stefan Lethagen, John Pasi, Frank G. H. Hill, Mohammad Bagher Hashemi‐Soteh, Luciano Baronciani, Christer Halldén, Andrea M. Guilliatt, Will Lester, I. R. Peake · 发表于：Blood · 年份：2006 · DOI：10.1182/blood-2006-05-020784 · 被引用次数：400 · 研究领域：Platelet Disorders and Treatments、Antiplatelet Therapy and Cardiovascular Diseases、Heparin-Induced Thrombocytopenia and Thrombosis

Type 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%.