title: Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome.
abstract: We report a novel case of gray platelet syndrome (GPS) where a severe deficiency of the platelet collagen receptor, glycoprotein (GP) VI, accompanies classical symptoms of a low platelet count and platelets lacking alpha-granules. Dense granules were normally present. Platelet aggregation with collagen was severely decreased, as was the response to convulxin (Cvx), a GPVI agonist. Quantitative analysis of GPVI using fluorescein isothiocyanate (FITC)-Cvx in flow cytometry showed its virtual absence on the patient's platelets. The GPVI deficiency was confirmed using monoclonal antibodies in Western blotting and in immunogold labeling on frozen thin sections where internal pools of GPVI were confirmed for normal platelets. The Fc receptor gamma-chain, constitutively associated with GPVI in normal platelets, was present in subnormal amounts, and the phospholipase C gamma 2-dependent activation pathway appeared to function normally. No autoantibodies to GPVI were found in the patient's serum using monoclonal antibody immobilization of platelet antigen (MAIPA). Sequencing of coding regions of the GPVI gene failed to show abnormalities, and mRNA for GPVI was present in the patient's platelets, pointing to a probable acquired defect in GPVI expression. Our results may provide a molecular explanation for the subgroup of patients with severely deficient collagen-induced platelet aggregation as previously described for GPS in the literature.
authors.affiliation: Institut Federatif de Recherche No. 4, Laboratoire d'Hematologie, Hopital Cardiologique, Pessac, France. paquita.nurden@cnrshl.u-bordeaux2.fr
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
authors.forename: Robert
authors.initials: R
authors.lastname: Combrié
authors.forename: Joelle
authors.initials: J
authors.lastname: Winckler
authors.forename: Veronique
authors.initials: V
authors.lastname: Arocas
authors.forename: Christelle
authors.initials: C
authors.lastname: Lecut
authors.forename: Jean-Max
authors.initials: JM
authors.lastname: Pasquet
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kunicki
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
mesh_terms: D001791:Blood Platelet Disorders / Q000097:blood* / Q000175:diagnosis; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D016022:Case-Control Studies; D003435:Crotalid Venoms / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type; D008854:Microscopy, Electron; D008875:Middle Aged; D010974:Platelet Aggregation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000172:deficiency* / Q000235:genetics; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D015398:Signal Transduction; D013577:Syndrome
chemical_list: D003435:Crotalid Venoms; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011961:Receptors, Fc; C028890:convulxin