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Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia

last modified Mar 21, 2017 08:55 AM

Dr Marloes Tijssen, Dr Ernest Turro, Prof Willem Ouwehand, and collaborators from Australia, France, and UK have discovered that mutations in the gene encoding tropomyosin 4 (TPM4) cause macrothrombocytopenia in humans.

Platelets are anuclear cells produced by large precursor cells called megakaryocytes. Platelets are vital for blood clotting, and the number and volume of platelets are independent risk factors for heart attack and stroke. Previous genome-wide association studies in nearly 70,000 individuals indicated that genetic variation in the TPM4 gene affect platelet count and volume. 

This study has identified two unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterised by low platelet count. Insufficient TPM4 expression in megakaryocytes resulted in a defect in the terminal stages of platelet production and had a mild effect on platelet function.

Together, the findings show a role for TPM4 in platelet biogenesis and reveal that truncating variants in TPM4 cause a previously undescribed dominant Mendelian platelet disorder.

Full article can be read here.

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