Bernard-Soulier syndrome: Novel nonsense mutation in GPIbβ gene affecting GPIb-IX complex expression

Bernard-Soulier syndrome (BSS) is a rare autosomal recessive genetic disorder characterized by thrombocytopenia, circulating giant platelets, and prolonged bleeding time. BSS is explained by a defect in primary hemostasis owing to quantitative or qualitative defect in the GPIb-IX-V complex, composed of four subunits: GPIbα, GPIbβ, GPIX, and GPV. In this study, we report a novel GPIbβ defect in a Tunisian family, in which Serine 23 is substituted by a Stop codon causing a premature termination of translation. This defect was homozygous in the BSS patient and heterozygote in both the parents and sisters of the patient. We studied the effect of this mutation on the expression of the GPIb-IX complex by western blot, flow cytometry, and confocal microscopy: GPIbα and GPIX were absent on the surface of platelets, whereas they were present in the cytoplasm. These results led to conclude that the novel Ser 23 Stop mutation in GPIbβ is responsible of BSS in the studied family and hampers the complex to form on the platelets surface. © Springer-Verlag 2008.