Document Detail


A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder.
MedLine Citation:
PMID:  19552682     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The physiological relevance of the collagen glycoprotein VI (GPVI) receptor was known prior to its recognition as a platelet membrane receptor as several patients lacking GPVI as a consequence of autoantibody inhibition presented with a mild bleeding diathesis. Remarkably, patients with a proven GPVI gene mutation have not yet been identified. RESULTS: In the present study, we describe a patient with a lifelong history of bleeding problems, structurally normal platelets but a functional platelet defect. Platelet aggregations are normal except for an absent response to Horm collagen, convulxin and the collagen-related peptide (CRP). ATP dense granule secretion is normal with ADP but absent with Horm collagen. Thrombus formation on a collagen surface in flowing blood is reduced but more single platelets are attached. Remarkably, the platelet function analyzer-100 shows a shortened collagen/ADP closure time. Flow cytometry demonstrates an absent expression of GPVI whereas immunoblot analysis shows strongly reduced levels of GPVI. The patient is compound heterozygous for an out-of-frame 16-bp deletion and a missense mutation S175N in a highly conserved residue of the 2nd Ig-like GPVI domain. The parents without clinical bleeding problems are heterozygous carriers. The mother carries the S175N mutation and presents with a mild functional platelet defect. In vitro studies show a reduced membrane expression and convulxin binding with the mutated S175N compared with the wild-type (WT) GPVI receptor. CONCLUSIONS: This study presents the first patient with a proven genetic GPVI defect.
Authors:
C Hermans; C Wittevrongel; C Thys; P A Smethurst; C Van Geet; K Freson
Publication Detail:
Type:  Case Reports; Journal Article     Date:  2009-06-22
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  7     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-13     Completed Date:  2009-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  1356-63     Citation Subset:  IM    
Affiliation:
Department of Haematology, Haemostasis and Thrombosis Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Coagulation Disorders / genetics*
Crotalid Venoms / metabolism
Family Health
Female
Heterozygote*
Humans
Lectins, C-Type / metabolism
Mutation*
Platelet Aggregation / genetics
Platelet Membrane Glycoproteins / genetics*
Protein Binding
Receptors, IgE / genetics
Chemical
Reg. No./Substance:
0/Crotalid Venoms; 0/Lectins, C-Type; 0/Platelet Membrane Glycoproteins; 0/Receptors, IgE; 0/platelet membrane glycoprotein VI; 37206-04-5/convulxin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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