Abstract
In the platelets of a type II Glanzmann thrombasthenia patient, the amount of glycoprotein (GP) IIb and IIIa was significantly reduced. Three novel mutations were identified in the GPIIb gene (c.440C->G/p.Leu116Val, c.1772_1773insG/p.Asp560GlyfsX16 and c.2438C->A/p.His782Asn). p.Leu116Val did not represent a causative mutation. The c.1772_1773insG mutation resulted in an early stop codon and non-sense mediated decay of mRNA. When expressed in transfected BHK cells, the truncated protein was unable to form complex with GPIIIa. The p.His782Asn mutation compromised transport of the pro-GPIIb/IIIa complex from the endoplasmic reticulum to the Golgi, hindering its maturation and surface expression.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Codon, Nonsense
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Cricetinae
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DNA Mutational Analysis
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Endoplasmic Reticulum / metabolism
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Fibrinogen / metabolism
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Genotype
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Golgi Apparatus / metabolism
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Humans
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Integrin alpha2 / chemistry
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Integrin alpha2 / genetics*
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Integrin beta3 / metabolism
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Male
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Mesocricetus
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Middle Aged
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Protein Binding
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Protein Interaction Mapping
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Protein Processing, Post-Translational / genetics
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Protein Structure, Tertiary
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Protein Transport / genetics
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Recombinant Fusion Proteins / metabolism
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Structure-Activity Relationship
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Thrombasthenia / genetics*
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Transfection
Substances
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Codon, Nonsense
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ITGA2B protein, human
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ITGB3 protein, human
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Integrin alpha2
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Integrin beta3
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Recombinant Fusion Proteins
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Fibrinogen