A Glanzmann thrombasthenia family associated with a TUBB1‐related macrothrombocytopenia
| Autor: | Alan T. Nurden, Benoît Guillet, Jacques Caen, Xavier Pillois, Sophie Bayart, Paquita Nurden |
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| Přispěvatelé: | CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Académie nationale de médecine, Centre de Traitement des Maladies Hémorragiques [CHU Rennes], Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Rhythmologie et de Modélisation Cardiaque [Bordeaux] (Plateforme Technologique d’Innovation Biomédicale), Hôpital Xavier Arnozan - CHU de Bordeaux, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
| Rok vydání: | 2019 |
| Předmět: |
[SDV]Life Sciences [q-bio]
thrombocytopenia membrane glycoproteins 030204 cardiovascular system & hematology Gene mutation 03 medical and health sciences symbols.namesake 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Gene expression Medicine Platelet Gene Sanger sequencing business.industry Glanzmann thrombasthenia Oligogenic Inheritance Hematology Phenotype 3. Good health Immunology gene expression symbols β-tubulin Complication business |
| Zdroj: | Journal of Thrombosis and Haemostasis Journal of Thrombosis and Haemostasis, Wiley, 2019, 17 (12), pp.2211-2215. ⟨10.1111/jth.14622⟩ Journal of Thrombosis and Haemostasis, 2019, 17 (12), pp.2211-2215. ⟨10.1111/jth.14622⟩ |
| ISSN: | 1538-7836 1538-7933 |
| DOI: | 10.1111/jth.14622 |
| Popis: | International audience; Background - Macrothrombocytopenia (MTP) is a rare but enigmatic complication of Glanzmann thrombasthenia (GT), an inherited bleeding disorder caused by the absence of platelet aggregation due to deficiencies of the αIIbβ3 integrin. Objectives - We report a family with type I GT and a prolonged bleeding time but unusually associated with congenital mild thrombocytopenia and platelet size heterogeneity with giant forms. Methods and results - Sanger sequencing of DNA from the propositus identified 2 heterozygous ITGB3 gene mutations: p.P189S and p.C210S both of which prevent αIIbβ3 expression and are causative of GT but without explaining the presence of enlarged platelets. High-throughput screening led to the detection of a predicted disease-causing heterozygous mutation in the TUBB1 gene: p.G146R, encoding β1-tubulin, a component of the platelet cytoskeleton and a gene where mutations are a known cause of MTP. Conclusions - Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically. |
| Databáze: | OpenAIRE |
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