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)
| Autor: | Ian R. Peake, Augusto B. Federici, Andrea Guilliatt, Jenny Goudemand, Francesco Rodeghiero, Lars Holmberg, Ulrich Budde, Jeroen Eikenboom, Giancarlo Castaman, Anne Goodeve, Mohammad Hashemi Soteh, Dominique Meyer, John Pasi, Luciano Baronciani, Stefan Lethagen, Jørgen Ingerslev, David Habart, Will Lester, Frank Hill, Claudine Mazurier, Reinhard Schneppenheim, Javier Batlle, Zdena Vorlova, Christer Halldén |
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| Rok vydání: | 2006 |
| Předmět: |
Male
DNA Mutational Analysis Gene mutation Biochemistry Gastroenterology Severity of Illness Index Cohort Studies Biopolymers Gene Frequency hemic and lymphatic diseases Surveys and Questionnaires Genotype Prevalence Missense mutation Family history Promoter Regions Genetic Blood coagulation test biology Hematology Europe von Willebrand Diseases Phenotype Female Blood Coagulation Tests congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Immunology Mutation Missense Hemorrhage ABO Blood-Group System Von Willebrand factor Internal medicine von Willebrand Factor medicine Von Willebrand disease Humans Point Mutation Allele frequency Alleles Family Health Factor VIII business.industry Cell Biology medicine.disease Health Surveys Amino Acid Substitution biology.protein RNA Splice Sites business |
| Zdroj: | Blood. 109(1) |
| ISSN: | 0006-4971 |
| Popis: | 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%. |
| Databáze: | OpenAIRE |
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