Genetic characterization of families with von Willebrand disease
Author
Summary, in English
When we investigated to what extent co-segregation exists in type 1 VWD, we found that the disease is linked to the VWF gene in a majority (27 of 31) of Swedish type 1 VWD families. Several common disease haplotypes probably exist for type 1 VWD in Sweden, which suggests founder effects. The Y1584C variation is not as common in the Swedish type 1 VWD population as it is in some other populations. We confirmed that blood group O is over-represented among type 1 VWD patients in Sweden. Apart from certain misunderstandings, the participants in the linkage study were found to have a satisfying level of knowledge of the genetics of the disease. In general, patients, younger individuals, and women have a higher knowledge about the genetics causing type 1 VWD than do healthy relatives, older individuals, and men, respectively.
Inherited recessively, the C570S mutation causes a distinct subtype of type 2A VWD characterized by very low plasma FVIII and VWF levels and the exclusive presence of the dimeric form of VWF in plasma. The findings define a structural element that is indispensable for VWF multimerization.
Inherited dominantly, the N1421K mutation causes type 2M VWD characterized by moderately decreased plasma FVIII and VWF levels, disproportionately low plasma VWF:RCo levels, and an apparently normal multimeric pattern. The findings indicate a structural element in the A1 domain that is necessary for proper GPIb binding.
Department/s
Publishing year
2008
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2008:89
Full text
Document type
Dissertation
Publisher
Department of Clinical Sciences, Lund University
Topic
- Cardiac and Cardiovascular Systems
Keywords
- mutation
- bleeding
- coagulation
- von Willebrand disease
- genetics
Status
Published
Research group
- Clinical Coagulation, Malmö
Supervisor
- Stefan Lethagen
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86059-42-2
Defence date
3 October 2008
Defence time
09:15
Defence place
Lilla aulan, MFC, ingång 59, Universitetssjukhuset MAS, Malmö
Opponent
- Riitta Lassila