title: 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.affiliation: The Academic Unit of Haematology, University of Sheffield, United Kingdom. a.goodeve@shef.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Goodeve
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Federici
authors.forename: Javier
authors.initials: J
authors.lastname: Batlle
authors.forename: Dominique
authors.initials: D
authors.lastname: Meyer
authors.forename: Claudine
authors.initials: C
authors.lastname: Mazurier
authors.forename: Jenny
authors.initials: J
authors.lastname: Goudemand
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.forename: Jorgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: David
authors.initials: D
authors.lastname: Habart
authors.forename: Zdena
authors.initials: Z
authors.lastname: Vorlova
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Lethagen
authors.forename: John
authors.initials: J
authors.lastname: Pasi
authors.forename: Frank
authors.initials: F
authors.lastname: Hill
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi Soteh
authors.forename: Luciano
authors.initials: L
authors.lastname: Baronciani
authors.forename: Christer
authors.initials: C
authors.lastname: Hallden
authors.forename: Andrea
authors.initials: A
authors.lastname: Guilliatt
authors.forename: Will
authors.initials: W
authors.lastname: Lester
authors.forename: Ian
authors.initials: I
authors.lastname: Peake
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D000483:Alleles; D019943:Amino Acid Substitution; D001704:Biopolymers; D001780:Blood Coagulation Tests; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005060:Europe; D005169:Factor VIII / Q000032:analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006306:Health Surveys; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014842:von Willebrand Diseases / Q000097:blood / Q000145:classification / Q000453:epidemiology* / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D001704:Biopolymers; D022821:RNA Splice Sites; D014841:von Willebrand Factor; D005169:Factor VIII