5/8/2023 0 Comments Diane kaplan orley healthnutGene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Collen, Désiré Deckmyn, Hans VandenDriessche, Thierry Pareyn, Inge Gillijns, Veerle Hebbel, Robert P. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factorĭe Meyer, Simon F. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. vWD also has a complex molecular pathogenesis. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD is a complex disease with clinical and genetic heterogeneity. Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). The molecular genetics of von Willebrand disease. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Serum measures of bone resorption were significantly decreased in G233V animals. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease
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