title: Platelets with a W127X mutation in GPIX express sufficient residual amounts of GPIbα to support adhesion to von Willebrand factor and collagen.
abstract: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder caused by a defect in the platelet glycoprotein (GP) Ib/IX complex. The GPIX W127X mutation is the most common genetic defect in Japanese patients with BSS, which is often misdiagnosed as immune thrombocytopenic purpura, presumably due to residual expression of GPIbα. Neither the mechanism by which this mutation leads to a mild bleeding diathesis, nor whether functional GPIbα is expressed on platelet surfaces is known. We investigated GPIbα expression and function in platelets with a GPIX W127X mutation (GPIXW127X). GPIbα complexed with GPIbβ by disulfide bonding was expressed on GPIXW127X platelets and stable CHO-K1 cells lacking GPIX but expressing GPIbα and GPIbβ. Expression of GPIbα/β on GPIXW127X platelets was sufficient to support adhesion to immobilized von Willebrand factor and type III collagen and ristocetin-induced platelet agglutination. A residual amount of functional GPIbα/β heteromer expressed on GPIXW127X platelets partially compensates for the absence of the GPIb/IX complex. This may account for the mild bleeding phenotype of the BSS variant characterized by a non-sense mutation in GPIX.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takata
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kanaji
authors.forename: Masaaki
authors.initials: M
authors.lastname: Moroi
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Seki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sano
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakazato
authors.forename: Eisaburo
authors.initials: E
authors.lastname: Sueoka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001606:Bernard-Soulier Syndrome / Q000175:diagnosis / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D016466:CHO Cells; D018389:Codon, Nonsense; D024061:Collagen Type III / Q000378:metabolism; D006224:Cricetinae; D003553:Cystine / Q000737:chemistry; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017354:Point Mutation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000175:diagnosis / Q000235:genetics; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012310:Ristocetin / Q000494:pharmacology; D014162:Transfection; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018389:Codon, Nonsense; D024061:Collagen Type III; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011993:Recombinant Fusion Proteins; C094990:adhesion receptor; D014841:von Willebrand Factor; D012310:Ristocetin; D003553:Cystine