A nonsense mutation in the GPIIb heavy chain (Ser 870->stop) impairs platelet GPIIb-IIIa expression

作者：Vinciguerra C; Khelif A; Alemany M; Morle F; Grenier C; Uzan G; Gulino D; Dechavanne M; Negrier C

来源：British Journal of Haematology, 1996, 95(2): 399-407.

DOI：10.1046/j.1365-2141.1996.d01-1903.x

• thrombocytopathy
• glycoprotein IIb
• integrin
• Glanzmann's thrombasthenia
• fibrinogen receptor

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, caused by a quantitative or qualitative defect of the GPIIb-IIIa integrin (alpha(IIb)beta(3)), which functions as the platelet fibrinogen receptor. We report a case of type I GT due to a homozygous mutation resulting in Ser 870 to stop codon substitution. This residue is located near the proteolytic cleavage site of proGPIIb. The mutation results in a GPIIb truncated of 138 amino acids, including transmembrane and intracytoplasmic domains, Cotransfection of an expression vector containing the mutant GPIIb and wild-type GPIIIa showed that the mutant Ser 870 --> stop GPIIb was able to associate to GPIIIa. However, this heterodimer failed to mature as shown by endoglycosidase-H digestion and was therefore not expressed at the COS-7 cell surface. This report is the first description of a homozygous nonsense mutation in the GPIIb gene and highlights the role of the GPIIb light chain.

• 出版日期1996-11