title: A new mutation, Ala1500-->Glu, responsible for type 2A von Willebrand disease.
abstract: 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 Willebrand factor (vWF) gene was obtained by polymerase chain reaction and then screened by denaturing gradient gel electrophoresis. The fragments displaying abnormal melting behavior were directly sequenced. A heterozygous C-->A substitution changing alanine 1500 to glutamic acid at position 4750 in the A2 domain of vWF was found. The structure of recombinant A1500E vWF within 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 absent in plasma but present in platelets. The mutation described here corresponds to the group II type 2A vWD characterized by normal secretion of all vWF multimers.
authors.affiliation: Thrombosis and Hemostasis Research Unit, Jiangsu Institute of Hematology, First Affiliated Hospital of Suzhou Medical College, Suzhou, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Wan
authors.forename: C
authors.initials: C
authors.lastname: Ruan
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001780:Blood Coagulation Tests; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D014842:von Willebrand Diseases / Q000145:classification / Q000235:genetics*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014841:von Willebrand Factor