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A novel candidate mutation (Arg 611 → His) in type I‘platelet discordant’von Willebrand's disease with desmopressin‐induced thrombocytopenia
Author(s) -
Castaman Giancarlo,
Eikenboom Jeroen C. J.,
Rodeghiero Francesco,
Briët Ernest,
Reitsma Pieter H.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb08383.x
Subject(s) - desmopressin , von willebrand factor , von willebrand disease , platelet membrane glycoprotein , platelet , mutation , coagulopathy , medicine , endocrinology , point mutation , allele , exon , glycoprotein ib , genetics , biology , gene
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 Arg 611 → 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 Arg 611 → His with the moderate thrombocytopenia observed after desmopressin infusion.