A Novel Hemizygous Bernard-Soulier Syndrome (BSS) Mutation in the Amino Terminal Domain of Glycoprotein (GP)Ibβ- Platelet Characterization and Transfection Studies

Summary

Glycoprotein (GP) Ib-V-IX is a unique adhesion receptor complex on platelets. Mutations in GPIbα, Ibβ, 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 GPIbβ allele is substituted by a Leu (GPIbβ: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 GPIbβ: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 GPIbα and GPIbβ from platelet lysates. Co-expression of GPIbβ:P29L with normal GPIbα and GPIX in a heterologous cell system confirmed that the mutant subunit did not support surface expression of the complex. Interestingly, residual expression of GPIbβ: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 GPIbβ is required for normal expression of the intact receptor complex.

Keywords

Platelets - glycoprotein - Bernard-Soulier

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