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bioRxiv · 10.1101/2025.02.11.637639

The membrane skeleton density of red blood cells in MYH9-related disease patients is decreased

Sun, S.·Pan, J.·Zhang, N.·Jin, X.·Zhu, T.-n.·Kang, Z.·Hao, J.·Li, X.-d.
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Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9 gene, which encodes the heavy chain of nonmuscle myosin IIA. Nearly all MYH9-RD patients present with macrothrombocytopenia, characterized by decreased platelet count and increased platelet size. In this study, we collected blood samples from three MYH9-RD patients (R702S, D1424N, and R1464C) and unexpectedly found that the actin levels in the red blood cells (RBCs) from all three MYH9-RD patients are substantially lower than the healthy controls. We further revealed that the levels of two RBC membrane skeleton proteins, -spectrin and tropomodulin, are also reduced in MYH9-RD RBCs. We showed that the membrane skeleton of MYH9-RD RBCs was more porous and that MYH9-RD RBCs produced more severe deformation under hyperosmotic pressure compared to healthy controls. We conclude that MYH9-RD mutations reduce the RBC membrane skeleton density and impair its mechanical properties, and propose that defects in the membrane skeleton network in RBCs may be a common symptom in MYH9-RD. Key pointsThe levels of membrane skeleton proteins and the density of membrane skeleton network in RBCs of MYH9-RD patients are reduced. MYH9-RD RBCs produce greater deformation under hypertonic conditions compared to healthy controls.

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Sun, S., Pan, J., Zhang, N., Jin, X., Zhu, T.-n., Kang, Z., Hao, J., Li, X.-d.. 2025-02-15. The membrane skeleton density of red blood cells in MYH9-related disease patients is decreased. https://doi.org/10.1101/2025.02.11.637639

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