Platelets with a W127X mutation in GPIX express sufficient residual amounts of GPIbα to support adhesion to von Willebrand factor and collagen

• Published in: International journal of hematology 2012-12, Vol.96 (6), p.733-742
• Main Authors: Takata, Yuka, Kanaji, Taisuke, Moroi, Masaaki, Seki, Ritsuko, Sano, Masayuki, Nakazato, Sachie, Sueoka, Eisaburo, Imamura, Yutaka, Okamura, Takashi
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibodies, Monoclonal - immunology; Bernard-Soulier Syndrome - diagnosis; Bernard-Soulier Syndrome - genetics; Biological and medical sciences; Blood Platelets - metabolism; CHO Cells; Codon, Nonsense; Collagen Type III - metabolism; Cricetinae; Cystine - chemistry; Diagnostic Errors; Female; Hematologic and hematopoietic diseases; Hematology; Humans; Medical sciences; Medicine; Medicine & Public Health; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Oncology; Original Article; Phenotype; Platelet Adhesiveness; Platelet diseases and coagulopathies; Platelet Glycoprotein GPIb-IX Complex - genetics; Platelet Glycoprotein GPIb-IX Complex - metabolism; Platelet Glycoprotein GPIb-IX Complex - physiology; Point Mutation; Pregnancy; Pregnancy Complications, Hematologic - diagnosis; Pregnancy Complications, Hematologic - genetics; Purpura, Thrombocytopenic, Idiopathic - diagnosis; Recombinant Fusion Proteins - physiology; Ristocetin - pharmacology; Transfection; von Willebrand Factor - metabolism
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-012-1216-5

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.