A Glanzmann thrombasthenia family associated with a TUBB1-related macrothrombocytopenia.

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. 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. 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. Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically. © 2019 International Society on Thrombosis and Haemostasis.

Citation

Benoit Guillet, Sophie Bayart, Xavier Pillois, Paquita Nurden, Jacques P Caen, Alan T Nurden. A Glanzmann thrombasthenia family associated with a TUBB1-related macrothrombocytopenia. Journal of thrombosis and haemostasis : JTH. 2019 Dec;17(12):2211-2215

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PMID: 31565851

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