SearchPublisher and Institutes
You are here: Home :: Area NEM :: Medical science :: Human medicine
Andrew Hillmann, Alan Nurden, Paquita Nurden, Robert Combri, Sgolne Claeyssens, Niamh Moran, Dermot Kenny
A Novel Hemizygous Bernard-Soulier Syndrome (BSS) Mutation in the Amino Terminal Domain of Glycoprotein (GP)Ib - Platelet Characterization and Transfection Studies
Glycoprotein (GP) Ib-V-IX is a unique adhesion receptor complex on platelets. Mutations in GPIb, Ib, and IX can lead to the rare bleeding disorder, Bernard-Soulier Syndrome (BSS). Here, we report a novel hemizygous variant of BSS in which Pro29 in one GPIb allele is substituted by a Leu (GPIb:P29L). Fluoresence in situ hybridisation revealed that the 22q11 locus was deleted from the homologous chromosome. The pedigree was determined and revealed inheritance of the GPIb:P29L allele from the father. Flow cytometry with a range of antibodies detected no expression of GPIb-V-IX on the surface of the patient's platelets. Western blotting revealed an absence of GPIb and GPIb from platelet lysates. Co-expression of GPIb:P29L with normal GPIb and GPIX in a heterologous cell system confirmed that the mutant subunit did not support surface expression of the complex. Interestingly, residual expression of GPIb:P29L anchored in the plasma membrane alone was now seen. This novel BSS mutation expressed in heterologous cells is in agreement with recent in vitro evidence that the correct conformation of the amino terminal region of GPIb is required for normal expression of the intact receptor complex.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 88, 12/2002
Pages: 1026 - 1032