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April 2024 QQ Summary: MYH9 Mutation

Our April 2024 Quick Question, “What PLT production abnormality is an MYH9 gene mutation?” attracted 26 responses. Here’s the distribution:

  1. Thrombocytopenia with absent radii [TAR]: 4 [15%]
  2. Bernard-Soulier syndrome [BSS]: 2 [7%]
  3. Immune thrombocytopenia [ITP]: 1 [4%]
  4. Wiskott-Aldrich syndrome: 1 [4%]
  5. May-Hegglin disorder: 18 [70%]

The production abnormalities are associated with mild to severe bleeding. TAR is a mutation in the RNA-binding protein 8A [RBM8A], a protein involved in nuclear mRNA splicing. BSS results from one of several mutations affecting the von Willebrand factor binding platelet receptor GP Ib/V/IX. In ITP, autoantibodies bind circulating platelets and bone marrow megakaryocytes, affecting platelet production and shortening platelet lifespan. Wiskott-Aldrich syndrome is an X-linked mutation associated with immunodeficiency and thrombocytopenia.

Click here for a comprehensive open-access review of platelet production abnormalities associated with mutations in the MYH9 gene: Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost. 2009;35:189–203. doi: 10.1055/s-0029-1220327.

Here’s an excerpt from the Althaus article: “Myosin heavy chain 9 (MYH9)-related platelet disorders belong to the group of inherited thrombocytopenias. The MYH9 gene encodes the nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cytoskeletal contractile protein. Several mutations in the MYH9 gene lead to the premature release of platelets from the bone marrow, macrothrombocytopenia, and cytoplasmic inclusion bodies within leukocytes. Four overlapping syndromes, known as May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian platelet syndrome, describe different clinical manifestations of MYH9 gene mutations.”
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