A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder

  title={A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder},
  author={C{\'e}dric Hermans and Christine Wittevrongel and Chantal Thys and Peter A. Smethurst and Chris Van Geet and Kathleen Freson},
  journal={Journal of Thrombosis and Haemostasis},
Summary.  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… 
An adenine insertion in exon 6 of human GP6 generates a truncated protein associated with a bleeding disorder in four Chilean families
To date, only two patients have been characterized at the molecular level who carry different compound heterozygous mutations in the GP6 gene, and the defect in most of the reported patients is acquired and associated with other diseases.
GP6 Haplotype of Missense Variants is Associated with Sticky Platelet Syndrome Manifested by Fetal Loss
  • M. Skerenova, J. Sokol, Z. Lasabová
  • Medicine, Biology
    Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
  • 2018
It is shown that haplotype PEAN associated with SPS and manifested by fetal loss is shown and suggested that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.
Laboratory investigation of platelet function in patients with mild bleeding disorders
This thesis built on the previous studies in the genotyping and platelet phenotyping project allowing further characterization of inherited platelet function defects in individuals with mild bleeding disorders, and evaluated three other platelet techniques by comparison with lumi-aggregometry to assess their overall potential in detecting plateletfunction defects.
Congenital platelet disorders and understanding of platelet function
Signalling pathway defects leading to agonist‐specific modifications of platelet aggregation are the current target of exome‐sequencing strategies and recent advances in the molecular characterization of Platelet function defects are reviewed.
Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.
One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand's disease.
Platelet glycoprotein VI genetic quantitative and qualitative defects
Platelet membrane glycoprotein VI is increasingly recognized as an important receptor for thrombus formation and growth and is compiled to compile data on the quantitative and qualitative genetic abnormalities of GPVI.
From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks.
Recent findings regarding the biological role of GPVI in platelet-related disorders are discussed and the efforts to develop potential therapeutic strategies based on its structure, signaling pathways, and biological effects are highlighted.
Phenotyping and genotyping of platelet defects in patient populations enriched in bleeding
The genetic basis of platelet defects was investigated in many of the patients, leading to identification of mutations in genes known to be critical in platelet biology, and identification of several possible novel variants.


Platelet glycoprotein VI‐related clinical defects
Clinical profiles of patients with familial or acquired GPVI defects are reviewed, revealing the bleeding defect is often severe and associated with immune dysfunction, and expression levels of platelet GPVI may be a marker of thrombotic risk.
A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion.
The results suggest that GPVI functions as a collagen receptor, and the serum from an idiopathic thrombocytopenic purpura patient contains a specific antibody against GPVI.
A familial platelet function disorder associated with abnormal signalling through the glycoprotein VI pathway
A familial case of abnormal platelet aggregation with dysfunctional signalling through GPVI that uniquely demonstrates divergent αIIbβ3‐activating and GPVI‐shedding pathways is reported, suggesting a signalling defect downstream of Syk.
The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression.
It is demonstrated for the first time that platelet function may be altered by allelic differences in GPVI, which can be specifically agonized by cross-linked collagen-related peptide (CRP-XL).
A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia.
Results indicated that platelet aggregation by the patient's IgG was induced by the reaction of an antibody with a specific antigen on the normal platelet membrane through stimulus-response coupling.
Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily.
The genes encoding human and mouse GPVI were identified and functional evidence demonstrating the identity of the recombinant protein with GPVI was shown, and it was demonstrated that the soluble protein blocks Cvx and collagen-induced platelet aggregation and that GPVI expression is restricted to megakaryocytes and platelets.
The TUBB 1 Q 43 P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure
The functional consequences of the platelet Q43P 1-tubulin substitution that is frequent in the healthy population and may protect men against arterial thrombosis are presented.
The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure.
The functional consequences of the platelet Q43P beta1-tubulin substitution that is frequent in the healthy population and may protect men against arterial thrombosis are presented.
Novel Platelet Membrane Glycoprotein VI Dimorphism Is a Risk Factor for Myocardial Infarction
The GP VI 13254CC genotype increases the risk of myocardial infarction, particularly in older individuals, and the interaction of the GPVI 13254C allele with other candidate risk alleles may accentuate this risk.