Compound heterozygous mutation in GPVI in a patient with a bleeding disorder. Export

@article{citeulike:5091580, abstract = {Background: The physiological relevance of the collagen glycoprotein VI (GPVI) receptor was known prior to its recognition as a platelet membrane receptor since several patients lacking GPVI as a consequence of autoantibody inhibition present with a mild bleeding diathesis. Remarkably, patients with a proven GPVI gene mutation could not yet been identified. Results: We here 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 while 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 2(nd) 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 to the wild type GPVI receptor. Conclusions: This study presents the first patient with a proven genetic GPVI defect.}, author = {Hermans, C. and Wittevrongel, C. and Thys, C. and Smethurst, P. A. and Van Geet, C. and Freson, K.}, citeulike-article-id = {5091580}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1538-7836.2009.03520.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19552682}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19552682}, day = {22}, doi = {10.1111/j.1538-7836.2009.03520.x}, issn = {1538-7836}, journal = {Journal of thrombosis and haemostasis : JTH}, keywords = {diagnosis, disorder, disorders, glycoprotein, glycoproteins, gpvi, receptor, review}, month = {June}, posted-at = {2009-07-08 10:59:00}, priority = {2}, title = {Compound heterozygous mutation in GPVI in a patient with a bleeding disorder.}, url = {http://dx.doi.org/10.1111/j.1538-7836.2009.03520.x}, year = {2009} }

TY - JOUR ID - citeulike:5091580 L3 - citeulike-article-id:5091580 N2 - Background: The physiological relevance of the collagen glycoprotein VI (GPVI) receptor was known prior to its recognition as a platelet membrane receptor since several patients lacking GPVI as a consequence of autoantibody inhibition present with a mild bleeding diathesis. Remarkably, patients with a proven GPVI gene mutation could not yet been identified. Results: We here 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 while 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 2(nd) 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 to the wild type GPVI receptor. Conclusions: This study presents the first patient with a proven genetic GPVI defect. JF - Journal of thrombosis and haemostasis : JTH SN - 1538-7836 TI - Compound heterozygous mutation in GPVI in a patient with a bleeding disorder. KW - diagnosis KW - disorder KW - disorders KW - glycoprotein KW - glycoproteins KW - gpvi KW - receptor KW - review AU - Hermans, C AU - Wittevrongel, C AU - Thys, C AU - Smethurst, PA AU - Van Geet, C AU - Freson, K PY - 2009/06/22/ UR - http://dx.doi.org/10.1111/j.1538-7836.2009.03520.x ER -