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A nonsense mutation in the GPIIb heavy chain (Ser 870 → stop) impairs platelet GPIIb–IIIa expression
Author(s) -
VINCIGUERRA C.,
KHELIF A.,
ALEMANY M.,
MORLE F.,
GRENIER C.,
UZAN G.,
GULINO D.,
DECHAVANNE M.,
NEGRIER C.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1903.x
Subject(s) - nonsense mutation , thrombasthenia , glanzmann's thrombasthenia , platelet , endoglycosidase h , mutation , microbiology and biotechnology , mutant , chemistry , platelet glycoprotein gpiib iiia complex , biology , biochemistry , gene , receptor , missense mutation , integrin , cell , immunology , platelet aggregation , golgi apparatus
Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, caused by a quantitative or qualitative defect of the GPIIb–IIIa integrin (α IIb β 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.