Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival
| Autor: | Stefana Gavazova, Michael Balistreri, Patricia A. Morateck, Joan Cox Gill, Marilyn J. Manco-Johnson, Sandra L. Haberichter, Daniel B. Bellissimo, Robert R. Montgomery, Pamela A. Christopherson |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Heterozygote congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty DNA Mutational Analysis Immunology Mutation Missense Gene mutation medicine.disease_cause Hemostasis Thrombosis and Vascular Biology Biochemistry Von Willebrand factor hemic and lymphatic diseases Internal medicine von Willebrand Factor medicine Von Willebrand disease Humans Protein Precursors Protein precursor Desmopressin Family Health Mutation Factor VIII biology business.industry Heterozygote advantage Cell Biology Hematology medicine.disease Phenotype Pedigree Survival Rate von Willebrand Diseases Endocrinology cardiovascular system biology.protein Female business Half-Life circulatory and respiratory physiology medicine.drug |
| Zdroj: | Blood. 108:3344-3351 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report 4 families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1 to 3 hours, whereas the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in 2 families, and W1144G in 2 families, neither of which has been previously reported. We show that the ratio of steady-state plasma VWFpp to VWF:Ag can be used to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach, and we propose to refer to this phenotype as type-1C VWD. |
| Databáze: | OpenAIRE |
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