Article

Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.

Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, UK.
Hamostaseologie (Impact Factor: 1.59). 02/2010; 30(1):29-38.
Source: PubMed

ABSTRACT Platelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals. The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). 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. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.

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    ABSTRACT: Although rare, the prevalence of inherited platelet function disorders (IPFD) is probably underestimated due to underdiagnosis [1]. IPFD are heterogeneous in severity, mechanisms, and frequency and few are characterized at the molecular level. While severe IPFD, like Glanzmann Thrombasthenia (GT) or Bernard-Soulier Syndrome (BSS), are now rather straightforward to identify, the diagnosis of most other forms is cumbersome and requires complex assaysThis article is protected by copyright. All rights reserved.
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