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

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. -->

ISSN:	0007-1048
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48ff0ef34692e6888f2c5ba3ed568d8d https://pubmed.ncbi.nlm.nih.gov/8904900
Rights:	CLOSED
Přírůstkové číslo:	edsair.doi.dedup.....48ff0ef34692e6888f2c5ba3ed568d8d
Autor:	A. Khelif, Georges Uzan, C. Grenier, Christine Vinciguerra, F. Morle, Claude Negrier, M. Alemany, Marc Dechavanne, D. Gulino
Rok vydání:	1996
Předmět:	Male congenital hereditary and neonatal diseases and abnormalities Adolescent Fibrinogen receptor Nonsense mutation Mutant Blotting Western Platelet Glycoprotein GPIIb-IIIa Complex Immunoglobulin light chain Polymerase Chain Reaction hemic and lymphatic diseases Thrombocytopathy medicine Humans Platelet Genetics Chemistry Glanzmann's thrombasthenia Homozygote Hematology medicine.disease Molecular biology Stop codon Mutation Codon Terminator circulatory and respiratory physiology Thrombasthenia
Zdroj:	British journal of haematology. 95(2)
ISSN:	0007-1048
Popis:	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.
Databáze:	OpenAIRE
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