Title: A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder
Authors: Hermans, C
Wittevrongel, C
Thys, Cindy
Smethurst, P. A
Van Geet, Christel
Freson, Kathleen # ×
Issue Date: Aug-2009
Publisher: Blackwell Pub.
Series Title: Journal of Thrombosis and Haemostasis vol:7 issue:8 pages:1356-1363
Abstract: 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.
ISSN: 1538-7933
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Research Group Experimental Neurology
× corresponding author
# (joint) last author

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