Type 2M vWD resulting from a lysine deletion within a four lysine residue repeat in the A1 loop of von Willebrand factor

Citation
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
Citations number
30
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
THROMBOSIS AND HAEMOSTASIS
ISSN journal
03406245 → ACNP
Volume
84
Issue
2
Year of publication
2000
Pages
188 - 194
Database
ISI
SICI code
0340-6245(200008)84:2<188:T2VRFA>2.0.ZU;2-U
Abstract
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.