title: Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB.
abstract: The defective von Willebrand Factor (vWF) in type IIA von Willebrand disease (vWD) has decreased binding affinity for platelet membrane glycoprotein Ib (GPIb) while in type IIB vWD, the abnormal vWF has increased affinity for this receptor. Segments of exon 28 of the vWF gene were amplified by the polymerase chain reaction and sequenced in two patients with type IIA and two patients with type IIB vWD. One type IIB patient showed an arginine to tryptophan substitution at amino acid residue 543 in the mature vWF and the other patient had a valine to methionine change at residue 553. Including these two new cases, substitutions at residues 543 and 553 now account for more than half of the documented mutations in patients with type IIB vWD. One patient with type IIA vWD showed an isoleucine to threonine change at amino acid 865. This substitution has been reported in another patient with type IIA vWD. The other patient showed a novel proline to serine change at residue 885. The C to T nucleotide transition which causes the amino acid change was not found in over 100 normal chromosomes tested by allele specific oligonucleotide hybridization and was linked to type IIA vWD in the family. This potential mutation is more carboxyterminal in the vWF subunit than other reported mutations in type IIA vWD. It is apparent that mutations associated with type IIA vWD are not as tightly grouped as defects in type IIB vWD, supporting the evidence that the type IIA vWD phenotype is generated by diverse mechanisms.
authors.affiliation: INSERM U. 143, Hôpital de Bicêtre, France.
authors.forename: G
authors.initials: G
authors.lastname: Piétu
authors.forename: A S
authors.initials: AS
authors.lastname: Ribba
authors.forename: L
authors.initials: L
authors.lastname: de Paillette
authors.forename: G
authors.initials: G
authors.lastname: Chérel
authors.forename: J M
authors.initials: JM
authors.lastname: Lavergne
authors.forename: B R
authors.initials: BR
authors.lastname: Bahnak
authors.forename: D
authors.initials: D
authors.lastname: Meyer
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D004247:DNA