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).

Abstract

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%.

• Authors: Anne Goodeve, Jeroen Eikenboom, Giancarlo Castaman, Francesco Rodeghiero, Augusto B Federici, Javier Batlle, Dominique Meyer, Claudine Mazurier, Jenny Goudemand, Reinhard Schneppenheim, Ulrich Budde, Jorgen Ingerslev, David Habart, Zdena Vorlova, Lars Holmberg, Stefan Lethagen, John Pasi, Frank Hill, Mohammad Hashemi Soteh, Luciano Baronciani, Christer Hallden, Andrea Guilliatt, Will Lester, Ian Peake
• Journal: Blood (Blood) Vol. 109 Issue 1 Pg. 112-21 (Jan 01 2007) ISSN: 0006-4971 [Print] United States
• PMID: 16985174 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• ABO Blood-Group System
• Biopolymers
• RNA Splice Sites
• von Willebrand Factor
• Factor VIII

Topics

• ABO Blood-Group System (genetics)
• Alleles
• Amino Acid Substitution
• Biopolymers
• Blood Coagulation Tests
• Cohort Studies
• DNA Mutational Analysis
• Europe
• Factor VIII (analysis)
• Family Health
• Female
• Gene Frequency
• Genotype
• Health Surveys
• Hemorrhage (epidemiology, etiology)
• Humans
• Male
• Mutation, Missense
• Phenotype
• Point Mutation
• Prevalence
• Promoter Regions, Genetic (genetics)
• RNA Splice Sites (genetics)
• Severity of Illness Index
• Surveys and Questionnaires
• von Willebrand Diseases (blood, classification, epidemiology, genetics)
• von Willebrand Factor (analysis, genetics)