Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations

Objective: MYH9 disorders are characterised by giant platelets, thrombocytopenia, and Döhle body-like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for non-muscle myosin heavy chain-IIA (NMMHC-IIA). MYH9 R702 mutations are highly associated with Alport manifestations and result in Epstein syndrome. The aim of our study was to determine the haematological characteristics of MYH9 disorders as a result of R702 mutations to aid in making a proper diagnosis. Patients and methods: Platelet size of patients with MYH9 disorders was determined as platelet diameter by microscopic observation of 200 platelets on stained peripheral blood smears. Double in situ hybridisation using a biotinylated oligo(dT) probe and immunofluorescence analysis of neutrophil NMMHC-IIA was performed on peripheral blood smears. Results: Patients carrying R702 mutations had significantly larger platelets than those with other MYH9 mutations. Although granulocyte inclusion bodies were mostly invisible on stained blood smears, immunofluorescence analysis for NMMHC-IIA showed an abnormal type II localisation in all neutrophils. We first showed that poly(A)+ RNA coincided with accumulated NMMHC-IIA at inclusion bodies in patients with MYH9 disorders. However, no condensation of poly(A)+ RNA at inclusion bodies was observed in patients with R702 mutations. Conclusion: Our study shows that R702 mutations result in especially large platelets and inclusion bodies being faint and mostly invisible on conventionally stained blood smears. We further demonstrated that poly(A)+ RNA content but not NMMHC-IIA accumulation is responsible for the morphological appearance/stainability of inclusion bodies on stained blood smears and the amount of poly(A)+ RNA is decreased in those with R702 mutations.