Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations
Open Access
- 27 August 2009
- journal article
- case report
- Published by American Society of Hematology in Blood
- Vol. 114 (9), 1900-1903
- https://doi.org/10.1182/blood-2009-03-213504
Abstract
The glycoprotein VI (GPVI)/FcRγ complex is a key receptor for platelet activation by collagen. We describe, for the first time, 2 genetic abnormalities in one patient. This 10-year-old girl presented ecchymoses since infancy, a prolonged bleeding time despite a normal platelet count and no antiplatelet antibodies. Collagen-induced platelet activation was null, whereas GPVI quantification by flow cytometry evidenced an incomplete deficiency. Immunoblotting showed an abnormal migration of residual GPVI, and no FcRγ defect. GPVI DNA sequencing revealed (1) an R38C mutation in exon 3 of one allele and (2) an insertion of 5 nucleotides in exon 4 of the other allele, leading to a premature nonsense codon and absence of the corresponding mRNA. Introduction of the R38C mutation into recombinant GPVI-Fc resulted in abnormal protein migration and a loss of collagen binding. Thus, this composite genetic GPVI deficiency and dysfunction cause absence of platelet responses to collagen and a mild bleeding phenotype.Keywords
This publication has 20 references indexed in Scilit:
- Platelet glycoprotein VI‐related clinical defectsBritish Journal of Haematology, 2007
- Diverging signaling events control the pathway of GPVI down-regulation in vivoBlood, 2007
- Controlled shedding of platelet glycoprotein (GP)VI and GPIb–IX–V by ADAM family metalloproteinasesJournal of Thrombosis and Haemostasis, 2007
- Selective Blockade of Glycoprotein VI Clustering on Collagen HelicesPublished by Elsevier BV ,2006
- Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VIBlood, 2006
- Identification of Residues within Human Glycoprotein VI Involved in the Binding to CollagenPublished by Elsevier BV ,2004
- Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibodyBlood, 2004
- Platelet-collagen interaction: is GPVI the central receptor?Blood, 2003
- The Platelet Collagen Receptor Glycoprotein VI Is a Member of the Immunoglobulin Superfamily Closely Related to FcαR and the Natural Killer ReceptorsPublished by Elsevier BV ,1999
- Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor γ‐chainFEBS Letters, 1997