CHARACTERIZATION OF TYPE 2N VON-WILLEBRAND DISEASE USING PHENOTYPIC AND MOLECULAR TECHNIQUES

von Willebrand factor (VWF) is a multimeric glycoprotein found in plas ma non covalently linked to factor Vm (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in VWF with a normal multimeric pattern, but with reduced binding to FVII I. We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with t ype 1 vWD, 32 with mild haemophilia A and one possible haemophilia A c arrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carr ier). DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of VWF were analysed. After di rect sequencing, and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appear s to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients.