Bernard-Soulier syndrome: novel nonsense mutation in GPIbbeta gene affecting GPIb-IX complex expression.

Abstract:

: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: GPIbalpha, GPIbbeta, GPIX, and GPV. In this study, we report a novel GPIbbeta 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: GPIbalpha 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 GPIbbeta is responsible of BSS in the studied family and hampers the complex to form on the platelets surface.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Hadjkacem B,Elleuch H,Gargouri J,Gargouri A

doi

10.1007/s00277-008-0611-8

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

465-72

issue

5

eissn

0939-5555

issn

1432-0584

journal_volume

88

pub_type

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