L. Hilbert et al., Type 2M vWD resulting from a lysine deletion within a four lysine residue repeat in the A1 loop of von Willebrand factor, THROMB HAEM, 84(2), 2000, pp. 188-194
Type 1 von Willebrand disease is characterized by a decreased plasma concen
tration of functionally normal von Willebrand factor (VWF) whereas type 2M
is characterised by an abnormal vWF displaying decreased affinity for plate
lets. In these two types of patients, the multimeric structure of vWF is no
rmal.
We report here the identification, in two unrelated families from the UK an
d Algeria, of an in-frame 3 bp deletion, at the heterozygous state! resulti
ng in the deletion of a lysine residue within a four lysine repeat at posit
ion 642-645 of the mature vWF subunit (del K1405-1408 in prepro vWF). The p
atients who have a discrepancy between vWF antigen level and vWF ristocetin
cofactor activity exhibited decreased ristocetin-induced binding but only
a slight decrease in the percentage of high molecular weight (HMW) multimer
s in plasma.
Recombinant vWF harbouring this deletion did not bind to platelet GPIb, in
the presence of ristocetin or botrocetin although the protein is multimeriz
ed. Consequently, this lysine deletion was considered as a type 2M vWD muta
tion.