Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease

摘要: Abstract Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of factor (vWF) patient platelets. Although the platelet glycoprotein (GP) Ib/IX complex known to constitute platelet's ristocetin-dependent receptor for vWF, a unique structural abnormality within this has not previously been identified in PT-vWD. Using polymerase chain reaction amplify genomic DNA coding alpha GP Ib (GP alpha) and then sequencing amplified following cloning into M13mp18 M13mp19 phage vectors, we have found single point mutation region PT-vWD resulting substitution valine glycine at residue 233. This vWF-binding likely exert significant influence on conformation protein. Competitive oligonucleotide primer assay showed homozygous wild-type pattern from 161 normal volunteers studied 6 phenotypically members family. All 7 affected family were heterozygous mutant allele. Platelet mRNA reverse-transcribed competitive similar expression alleles patients. Absence population, tight linkage with phenotypic disease, absence any additional these patients identify glycine-to-valine as underlying functional vWF