title: A novel candidate mutation (Arg611-->His) in type I 'platelet discordant' von Willebrand's disease with desmopressin-induced thrombocytopenia.
abstract: In three affected members of a family with type I 'platelet discordant' von Willebrand's disease displaying desmopressin-induced thrombocytopenia, we have detected in exon 28 of the von Willebrand factor gene a heterozygous G(4121)-->A transition, which predicts an Arg611-->His substitution. The mutated allele was absent in 50 normal individuals. An unrelated patient with a similar phenotype was also found to be heterozygous for this mutation. The mutation is located in the A1 domain of von Willebrand factor, where most type 2B von Willebrand's disease mutations are found. Mutations in this domain result in von Willebrand factor multimers with enhanced affinity for platelet glycoprotein Ib, and this may explain the association of Arg611-->His with the moderate thrombocytopenia observed after desmopressin infusion.
authors.affiliation: Department of Haematology, University Hospital, Leiden, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: J C
authors.initials: JC
authors.lastname: Eikenboom
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: E
authors.initials: E
authors.lastname: Briët
authors.forename: P H
authors.initials: PH
authors.lastname: Reitsma
mesh_terms: D001483:Base Sequence; D003894:Deamino Arginine Vasopressin / Q000009:adverse effects*; D006801:Humans; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D017354:Point Mutation; D013921:Thrombocytopenia / Q000139:chemically induced / Q000235:genetics*; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin