Recombinant expression of mutations causing von Willebrand disease type Normandy: characterization of a combined defect of factor VIII binding and multimerization

摘要: Von Willebrand disease type Normandy (VWD 2N) is caused by mutations at the factor VIII (FVIII) binding site of VWF, located amino-terminus mature VWF. It inherited in a recessive fashion and both homozygous compound heterozygous have been identified. Homozygous are correlated with clinical phenotype indistinguishable from mild hemophilia A conventional laboratory tests, whereas heterozygosity quantitative defect may appear as VWD 1 (VWD1).We now identified expressed novel mutation (Y795C) which responsible for both, defective FVIII-binding aberrant multimers female patient FVIII deficiency. Additionally we another (E787K), previously us male severe ‘pseudohemophilic’ phenotype. Analysis multimer structure respective recombinant VWF mutants reproduced observed phenotype: addition to Y795C only, E787K. Our results demonstrate causative nature two emphasize impact ‘cysteine mutations’ on