Summary
Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to
quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex,
the platelet receptor for von Willebrand factor. This complex is composed of four
subunits, GPIbα, GPIbβ, GPIX and GPV. We describe here the genetic basis of the disorder
in a patient with BSS. Flow cytometric analysis of the patient’s platelets showed
greatly reduced GPIbα and GPIX surface expression. Immunoblot analysis disclosed absence
of GPIbα, GPIbβ and GPIX in the platelets. DNA sequencing analysis revealed a novel
missense mutation in the GPIbβ gene that converts Pro (CCG) to Arg (CGG) at residue
74. Homozygosity of the mutation was confirmed by allele-specific restriction analysis,
chromosome 22 microsatellite analysis and quantitative Southern blotting. The mutant
GPIbβ was normally transcribed. Transient transfection studies confirmed that mutant
GPIbβ impairs surface expression of GPIb/IX, showing that the mutation is responsible
for a BSS phenotype observed in the patient.
Keywords
Bernard-Soulier syndrome - chromosome 22 - giant platelets - glycoprotein Ibβ - thrombocytopenia