title: A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of Arg854 by Gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.
abstract: We describe a patient with a lifelong bleeding disorder previously classified as von Willebrand's disease (vWD) type I. The factor VIII (FVIII) level in this patient was disproportionately low and we showed that this was due to a decreased factor VIII binding capacity of her vWF. To characterize the molecular defect in this type of vWD, a cDNA-dependent polymerase chain reaction (PCR) amplification was performed using platelet RNA as a template. Direct sequencing of the amplified fragment, which encodes for the FVIII-binding domain, showed a single nucleotide change in exon 20 at codon 854, resulting in the substitution of CAG glutamine (Gln) for CGG arginine (Arg). At the level of the cDNA only the mutated sequence was found, whereas at genomic DNA level the patient was heterozygous for this mutation. This patient is therefore a compound heterozygote for a point mutation resulting in a FVIII-binding defect and a vWF allele with low transcript levels.
authors.affiliation: Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Peerlinck
authors.forename: J C
authors.initials: JC
authors.lastname: Eikenboom
authors.forename: H K
authors.initials: HK
authors.lastname: Ploos Van Amstel
authors.forename: W
authors.initials: W
authors.lastname: Sangtawesin
authors.forename: J
authors.initials: J
authors.lastname: Arnout
authors.forename: P H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: J
authors.initials: J
authors.lastname: Vermylen
authors.forename: E
authors.initials: E
authors.lastname: Briët
mesh_terms: D000328:Adult; D000483:Alleles; D001120:Arginine / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005973:Glutamine / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014841:von Willebrand Factor; D005973:Glutamine; D005169:Factor VIII; D001120:Arginine