A NOVEL CANDIDATE MUTATION (ARG(6LL)-]HIS) IN TYPE-I PLATELET DISCORDANT VON WILLEBRANDS DISEASE WITH DESMOPRESSIN-INDUCED THROMBOCYTOPENIA

In three affected members of a family with type I 'platelet discordant ' von Willebrand's disease displaying desmopressin-induced thrombocyto penia, 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 individu als. An unrelated patient with a similar phenotype was also found to b e heterozygous for this mutation. The mutation is located in the Al do main of von Willebrand factor, where most type 2B von Willebrand's dis ease mutations are found, Mutations in this domain result in von Wille brand factor multimers with enhanced affinity for platelet glycoprotei n Ib, and this may explain the association of Arg(611) --> His With th e moderate thrombocytopenia observed after desmopressin infusion.