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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1900-1903. Prepublished online as a Blood First Edition Paper on June 23, 2009; DOI 10.1182/blood-2009-03-213504. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-03-213504v1 114/9/1900    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Dumont, B. Articles by Jandrot-Perrus, M. PubMed PubMed Citation Articles by Dumont, B. Articles by Jandrot-Perrus, M. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Brief Report Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations Bénédicte Dumont1,2, Dominique Lasne3,4, Chantal Rothschild5, Maxime Bouabdelli1, Véronique Ollivier1, Claire Oudin6, Nadine Ajzenberg1,2, Bernard Grandchamp6, and Martine Jandrot-Perrus1,2 1 Inserm, U698, Hôpital Bichat, Paris; 2 Laboratoire d'Hématologie, Hôpital Bichat, Assistance Publique-Hopitaux de Paris (AP-HP), Paris; 3 Service d'Hématologie Biologique, Hôpital Necker, AP-HP, Paris; 4 Inserm, U765, Paris; 5 Centre d'Hémophilie, Hôpital Necker, AP-HP, Paris; and 6 Biochimie B, Hôpital Bichat, AP-HP, Paris, France The glycoprotein VI (GPVI)/FcR 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 FcR 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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