A new mutation, Ala1500 -> Glu, responsible for type 2A von Willebrand disease

Two patients (from the same family) with a bleeding disorder were diagnosed with type 2A von Willebrand disease (vWD). The 28th exon of the von Willeb rand factor (vWF) gene was obtained by polymerase chain reaction and then s creened by denaturing gradient gel electrophoresis. The fragments displayin g abnormal melting behavior were directly sequenced. A heterozygous C --> A substitution changing alanine 1500 to glutamic acid at position 4750 in th e A2 domain of vWF was found. The structure of recombinant A1500E vWF withi n transfected COS-7 cells and the secretion of high-molecular-weight (HMW) multimers were similar to wild-type vWF. HMW forms of vWF multimers were ab sent in plasma but present in platelets. The mutation described here corres ponds to the group II type 2A vWD characterized by normal secretion of all vWF multimers. Int J Hematol. 2000;72:512-516. (C)2000 The Japanese Society of Hematology.