TY - JOUR
T1 - 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)
AU - Goodeve, Anne
AU - Eikenboom, Jeroen
AU - Castaman, Giancarlo
AU - Rodeghiero, Francesco
AU - Federici, Augusto B.
AU - Batlle, Javier
AU - Meyer, Dominique
AU - Mazurier, Claudine
AU - Goudemand, Jenny
AU - Schneppenheim, Reinhard
AU - Budde, Ulrich
AU - Ingerslev, Jorgen
AU - Habart, David
AU - Vorlova, Zdena
AU - Holmberg, Lars
AU - Lethagen, Stefan
AU - Pasi, John
AU - Hill, Frank
AU - Hashemi Soteh, Mohammad
AU - Baronciani, Luciano
AU - Halldén, Christer
AU - Guilliatt, Andrea
AU - Lester, Will
AU - Peake, Ian
PY - 2007
Y1 - 2007
N2 - 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%.
AB - 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%.
U2 - 10.1182/blood-2006-05-020784
DO - 10.1182/blood-2006-05-020784
M3 - Article
VL - 109
SP - 112
EP - 121
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -