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Semin Thromb Hemost 2009; 35(2): 204-212
DOI: 10.1055/s-0029-1220328
© Thieme Medical Publishers

Genetic Testing in the Diagnostic Evaluation of Inherited Platelet Disorders

Alan T. Nurden1 , Mathieu Fiore1 , Xavier Pillois1 , Paquita Nurden1
  • 1Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Pessac, France
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Publication History

Publication Date:
30 April 2009 (online)

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ABSTRACT

Inherited disorders of platelets give rise to rare bleeding syndromes through defects of platelet function and/or platelet production. Platelet function testing by biological and immunologic assays can identify the loss or abnormal functioning of specific receptor systems, signaling pathways, storage organelles, or enzymatic activities essential for adhesion, activation, and aggregation. In vitro culture of megakaryocytes can help identify the origin of familial thrombocytopenias, and electron microscopy can point to ultrastructural defects and giant platelet syndromes. But a full diagnosis can only be complete when the genetic defect has been defined for each patient. Glanzmann thrombasthenia (GT) and the Bernard-Soulier syndrome are the most studied of the membrane disorders and a wide range of mutations identified. We will use GT as an example to show how genetic studies can help understand the cell biology, pathophysiology, and management of a group of rare diseases where many of the genetic causes remain to be elucidated. Knowledge of the mutation in GT and whether it affects either of the ITGA2B or ITGB3 genes will be essential as we enter the period where accurate prenatal diagnosis and gene therapy may become viable options.

KEYWORDS

Inherited platelet disorders - bleeding syndrome - genetic testing - Glanzmann thrombasthenia - integrin αIIbβ3

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Dr. Alan T Nurden

Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale

Hôpital Xavier Arnozan, Pessac 33600, France

Email: Alan.Nurden@cnrshl.u-bordeaux2.fr

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