Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations

被引:35
作者
Kunishima, Shinji
Yoshinari, Miyako
Nishio, Hisanori
Ida, Komei
Miura, Takuma
Matsushita, Tadashi
Hamaguchi, Motohiro
Saito, Hidehiko
机构
[1] Natl Hosp Org, Nagoya Med Ctr, Cin Res Ctr, Dept Haemostasis,Naka Ku, Nagoya, Aichi 4600001, Japan
[2] Tohoku Univ, Inst Dev Aging & Canc, Dept Paediat Oncol, Sendai, Miyagi, Japan
[3] Miyazaki Prefectural Hosp, Dept Paediat, Miyazaki, Japan
[4] Univ Tokyo, Dept Paediat, Tokyo, Japan
[5] Tochigi Hosp, Natl Hosp Org, Dept Paediat, Utsunomiya, Tochigi, Japan
[6] Nagoya Univ, Dept Haematol Oncol, Nagoya, Aichi, Japan
[7] JR Tokai Cent Hosp, Nagoya, Aichi, Japan
关键词
Epstein syndrome; macrothrombocytopenia with leukocyte inclusions; MYH9; disorders; non-muscle myosin heavy chain-IIA; ribonucleoprotein complex;
D O I
10.1111/j.1600-0609.2006.00806.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: MYH9 disorders are characterised by giant platelets, thrombocytopenia, and Dohle 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.
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页码:220 / 226
页数:7
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