Losonczy Gergely, Rosenberg Nurit, Boda Zoltán, Vereb György, Kappelmayer János, Hauschner Hagit, Bereczky Zsuzsanna, Muszbek László
Clinical Research Center, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
Haematologica. 2007 May;92(5):698-701. doi: 10.3324/haematol.10847.
In the platelets of a type II Glanzmann thrombasthenia patient, the amount of glycoprotein (GP) IIb and IIIa was significantly reduced. Three novel mutations were identified in the GPIIb gene (c.440C->G/p.Leu116Val, c.1772_1773insG/p.Asp560GlyfsX16 and c.2438C->A/p.His782Asn). p.Leu116Val did not represent a causative mutation. The c.1772_1773insG mutation resulted in an early stop codon and non-sense mediated decay of mRNA. When expressed in transfected BHK cells, the truncated protein was unable to form complex with GPIIIa. The p.His782Asn mutation compromised transport of the pro-GPIIb/IIIa complex from the endoplasmic reticulum to the Golgi, hindering its maturation and surface expression.
在一名II型Glanzmann血小板无力症患者的血小板中，糖蛋白（GP）IIb和IIIa的量显著减少。在GPIIb基因中鉴定出三个新的突变（c.440C->G/p.Leu116Val、c.1772_1773insG/p.Asp560GlyfsX16和c.2438C->A/p.His782Asn）。p.Leu116Val不代表致病突变。c.1772_1773insG突变导致提前终止密码子和mRNA的无义介导衰变。当在转染的BHK细胞中表达时，截短的蛋白无法与GPIIIa形成复合物。p.His782Asn突变损害了前GPIIb/IIIa复合物从内质网到高尔基体的转运，阻碍了其成熟和表面表达。
