title: Identification of a new type 2M von Willebrand disease mutation also at position 1324 of von Willebrand factor.
abstract: Type 2M von Willebrand disease (VWD) refers to variants with decreased platelet-dependent function that is not associated with the loss of high molecular weight (HMW) von Willebrand factor (VWF) multimers. This category includes the so-called "phenotype B" responsible for inexistent ristocetin-induced but normal botrocetin-induced binding of VWF to platelet glycoprotein lb. The missense mutation G1324S was identified in the first patient reported to display "phenotype B". We report here on the identification in four members of a French family of a missense mutation also affecting this glycine residue but changing it into an alanine residue. These individuals are heterozygous for this mutation and two of them display an additional quantitative VWF deficiency resulting from a stop codon at position 2470. After transient transfection in Cos-7 cells, the mutated recombinant protein harbouring the G1324A substitution was shown to exhibit normal multimers and inexistent ristocetin-induced but normal botrocetin-induced binding to GPIb, confirming the classification of this new mutation as a type 2M VWD mutation.
authors: Unité de Développement Préclinique, LFB, Lille, France. hilbert@lfb.fr
authors: L
authors: L
authors: Hilbert
authors: E
authors: E
authors: Fressinaud
authors: A S
authors: AS
authors: Ribba
authors: D
authors: D
authors: Meyer
authors: C
authors: C
authors: Mazurier
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000818:Animals; D001704:Biopolymers; D019556:COS Cells; D002522:Chlorocebus aethiops; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005602:France; D006470:Hemorrhage / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012310:Ristocetin / Q000494:pharmacology; D014162:Transfection; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D001704:Biopolymers; D003062:Codon; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D012310:Ristocetin