title: Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia.
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.
authors.affiliation: Clinical Research Center, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Losonczy
authors.forename: Nurit
authors.initials: N
authors.lastname: Rosenberg
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Boda
authors.forename: György
authors.initials: G
authors.lastname: Vereb
authors.forename: János
authors.initials: J
authors.lastname: Kappelmayer
authors.forename: Hagit
authors.initials: H
authors.lastname: Hauschner
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bereczky
authors.forename: László
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D000818:Animals; D002460:Cell Line; D018389:Codon, Nonsense; D006224:Cricetinae; D004252:DNA Mutational Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000737:chemistry / Q000235:genetics*; D039661:Integrin beta3 / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013915:Thrombasthenia / Q000235:genetics*; D014162:Transfection
chemical_list: D018389:Codon, Nonsense; C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3; D011993:Recombinant Fusion Proteins; D005340:Fibrinogen