The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study
- 10 August 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (1), 145-154
- https://doi.org/10.1182/blood-2006-05-021105
Abstract
In order to evaluate the changes within the VWF gene that might contribute to the pathogenesis of type 1 von Willebrand disease (VWD), a large multicenter Canadian study was undertaken. We present data from the sequence analysis of the VWF gene in 123 type 1 VWD index cases and their families. We have identified putative mutations within the VWF gene in 63% (n = 78) of index cases, leaving 37% (n = 45) with no identified changes. These changes comprise 50 different putative mutations: 31 (62%) missense mutations, 8 (16%) changes involving the VWF transcriptional regulatory region, 5 (10%) small deletions/insertions, 5 (10%) splicing consensus sequence mutations, and 1 nonsense mutation. Twenty-one of the index cases had more than one putative VWF mutation identified. We were somewhat more likely to identify putative mutations in cases with lower VWF levels, and the contribution of other factors, such as ABO blood group, seems more important in milder cases. Taken as a whole, our data support a complex spectrum of molecular pathology resulting in type 1 VWD. In more severe cases, genetic changes are common within the VWF gene and are highly penetrant. In milder cases, the genetic determinants are more complex and involve factors outside of the VWF gene.Keywords
This publication has 36 references indexed in Scilit:
- Genetic linkage and association analysis in type 1 von Willebrand disease: results from the Canadian Type 1 VWD StudyJournal of Thrombosis and Haemostasis, 2006
- Evaluation of the von Willebrand factor Y1584C polymorphism as a potential risk factor for bleeding in patients receiving anticoagulant treatment with vitamin K antagonistsJournal of Thrombosis and Haemostasis, 2005
- An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13Blood, 2004
- Founder von Willebrand factor haplotype associated with type 1 von Willebrand diseaseBlood, 2003
- Von Willebrand disease type 1: a diagnosis in search of a diseaseBlood, 2003
- Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African‐American womenAmerican Journal of Hematology, 2001
- Prevalence of von Willebrand disease in children: A multiethnic studyThe Journal of Pediatrics, 1993
- Amino acid sequence of human von Willebrand factorBiochemistry, 1986
- Human von Willebrand Factor (vWF): Isolation of Complementary DNA (cDNA) Clones and Chromosomal LocalizationScience, 1985
- Molecular cloning of cDNA for human von willebrand factor: Authentication by a new methodCell, 1985