New variant of von Willebrand disease type II with markedly increased levels of von Willebrand factor antigen and dominant mode of inheritance: von Willebrand disease type IIC Miami
| Autor: | J E Sadler, Rabinowitz I, M R Ledford, Jessie W. Kent, Civantos F |
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| Rok vydání: | 1993 |
| Předmět: |
Proband
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Mutation biology medicine.diagnostic_test Immunology Cell Biology Hematology medicine.disease medicine.disease_cause Biochemistry Exon Endocrinology Von Willebrand factor Bleeding time hemic and lymphatic diseases Internal medicine medicine biology.protein Coagulopathy Von Willebrand disease Platelet circulatory and respiratory physiology |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | A variant of von Willebrand disease (vWD) was identified in six members of a kindred spanning four generations. The proband was a 46-year-old woman with a lifelong history of bleeding, a prolonged bleeding time (> 15 minutes), markedly elevated von Willebrand factor (vWF) antigen (vWF:Ag = 2.09 U/mL), slightly reduced ristocetin cofactor activity, and a plasma vWF multimer pattern similar to that of vWD type IIC. Similar findings were observed in her three children, mother, and brother. In affected family members, platelet and plasma vWF multimer patterns were discrepant with higher molecular weight multimers observed in platelet vWF. Following a 1-Des-amino-8-D-arginine vasopressin (DDAVP) challenge, the proband failed to normalize her bleeding time even though vWF: Ag rose by 70% and higher molecular weight multimers were increased slightly. Genetic studies were consistent with autosomal dominant inheritance of a mutation within the vWF gene. By sequencing of cloned genomic DNA, mutations were excluded in exons 4, 5, 14, and 15, which encode regions of the vWF propeptide proposed to be important in multimer biosynthesis. Mutations also were excluded in exons 28 to 31, which encompass the known mutations that cause vWD types IIA, IIB, and B. This new variant of vWD, characterized by autosomal dominant inheritance, a qualitative defect that resembles vWD type IIC, and increased plasma vWF:Ag, was tentatively designated vWD type IIC Miami. |
| Databáze: | OpenAIRE |
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