title: Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haemostasis and Thrombosis, Clinical Research Centre, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan. kunishis@nnh.hosp.go.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshinari
authors.forename: Hisanori
authors.initials: H
authors.lastname: Nishio
authors.forename: Komei
authors.initials: K
authors.lastname: Ida
authors.forename: Takuma
authors.initials: T
authors.lastname: Miura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
mesh_terms: D001120:Arginine / Q000235:genetics* / Q000378:metabolism; D001791:Blood Platelet Disorders / Q000235:genetics / Q000473:pathology; D001792:Blood Platelets / Q000473:pathology*; D048429:Cell Size; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007223:Infant; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011061:Poly A / Q000235:genetics; D013922:Thrombocytosis / Q000235:genetics* / Q000473:pathology*
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D011061:Poly A; D001120:Arginine; D018995:Myosin Heavy Chains