PMID: 15377475Sep 21, 2004Paper

A new candidate mutation, G1629R, in a patient with type 2A von Willebrand's disease: basic mechanisms and clinical implications

Haematologica
Lysiane HilbertClaudine Mazurier

Abstract

Type 2A von Willebrand's disease (VWD) refers to disease variants with decreased platelet-dependent function of von Willebrand factor (VWF) associated with the absence of high molecular weight (HMW) multimers. The candidate G1629R mutation, identified in an Italian patient with type 2A VWD, was expressed to confirm the relationship between phenotype and genotype. Plasma samples from the patient were studied after DDAVP or FVIII/VWF concentrate injections. Furthermore, an expression vector carrying the G1629R mutation was constructed by site-directed mutagenesis and transiently expressed in Cos-7 cells. The characteristics of the corresponding recombinant protein were analyzed. After 1-deamino-8-D-argine vasopressin (DDAVP) infusion, factor VIII and VWF activities increased and HMW VWF multimers were transiently observed in the patient's plasma. VWF activity increased only after administration of a dual FVIII/VWF concentrate. ADAMTS-13 activity did not change significantly before or after the therapies. Secretion, in culture medium, of the corresponding mutated protein (R1629-rVWF) was slightly decreased and this rVWF contained intermediate and HMW multimers. Furthermore, binding of R1629-rVWF to platelet GPIb was moderately red...Continue Reading

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