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An Arg 545 → Cys 545 substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease
Author(s) -
Donnér Mikael,
Andersson AnnMari,
Kristoffersson AnnCharlotte,
Nilsson Inga Marie,
Dahlbäck Björn,
Holmberg Lars
Publication year - 1991
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1991.tb01858.x
Subject(s) - von willebrand factor , von willebrand disease , platelet , platelet membrane glycoprotein , chemistry , mutation , platelet glycoprotein gpib ix complex , microbiology and biotechnology , biology , immunology , biochemistry , gene
Abstract: Type IIB is a special variant of von Willebrand's disease, characterized by an abnormal von Willebrand factor which shows an increased interaction with platelets. This interaction sometimes causes platelet aggregation and thrombocytopenia in vivo. It involves the glycoprotein‐Ib (GPIb) receptor on platelets and corresponding GPIb‐binding sites in the von Willebrand factor. We here demonstrate a C ± T mutation at codon 1308 of the von Willebrand factor gene in 2 related patients with IIB von Willebrand's disease. The transition gives rise to a substitution of arginine by cysteine at position 545 of the mature von Willebrand factor subunit. This position is close to the GPIb‐ as well as the collagen‐ and heparin‐binding domains of the von Willebrand factor. The mutation may change the conformation of the molecule in this region and activate the GPIb‐binding domain, which is normally not exposed in the von Willebrand factor of circulating blood.