A nonsense mutation in the GPIIb heavy chain (Ser 870-->stop) impairs platelet GPIIb-IIIa expression.

Abstract:

:Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, caused by a quantitative or qualitative defect of the GPIIb-IIIa integrin (alpha IIb beta 3), which functions as the platelet fibrinogen receptor. We report a case of type I GT due to a homozygous mutation resulting in Ser 870 to stop codon substitution. This residue is located near the proteolytic cleavage site of proGPIIb. The mutation results in a GPIIb truncated of 138 amino acids, including transmembrane and intracytoplasmic domains. Cotransfection of an expression vector containing the mutant GPIIb and wild-type GPIIIa showed that the mutant Ser 870-->stop GPIIb was able to associate to GPIIIa. However, this heterodimer failed to mature as shown by endoglycosidase-H digestion and was therefore not expressed at the COS-7 cell surface. This report is the first description of a homozygous nonsense mutation in the GPIIb gene and highlights the role of the GPIIb light chain.

journal_name

Br J Haematol

authors

Vinciguerra C,Khelif A,Alemany M,Morle F,Grenier C,Uzan G,Gulino D,Dechavanne M,Negrier C

doi

10.1046/j.1365-2141.1996.d01-1903.x

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

399-407

issue

2

eissn

0007-1048

issn

1365-2141

journal_volume

95

pub_type

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