Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia

Abstract

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.Asp560 GlyfsX16 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 nonsense 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. ©2007 Ferrata Storti Foundation.