2005 Fiscal Year Final Research Report Summary
Establishment of differential diagnostic method for MYH9 disorders and characterization of mechanisms of leukocyte inclusion formation
| Project/Area Number |
16590971
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | National Hospital Organization Nagoya Medical Center, Clinical Research Center |
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Principal Investigator |
KUNISHIMA Shinji National Hospital Organization Nagoya Medical Center, Clinical Research Center, Chief, 止血血栓研究部, 室長 (60373495)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Hidehiko National Hospital Organization Nagoya Medical Center, Clinical Research Center, President, 院長 (20153819)
HAMAGUCHI Motohiro National Hospital Organization Nagoya Medical Center, Clinical Research Center, Head, 部長 (30393177)
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| Project Period (FY) |
2004 – 2005
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| Keywords | May-Hegglin anomaly / MYH9 disorders / NMMHCA / Congenital platelet disorders / Congenital thrombocytopenia |
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| Research Abstract |
We developed an immunofluorescence technique for nonmuscle myosin heavy chain-IIA (NMMHCA) as a diagnostic method for the autosomal dominant macrothrombocytopenia with leukocyte inclusions, the MYH9 disorders, including May-Hegglin anomaly, Sebastian syndrome and Fechtner syndrome. We studied the neutrophil NMMHCA localization in 10 patients with MYH9 disorders. In five cases, leukocyte inclusion bodies were observed on May-Grunwald-Giemsa stained peripheral blood smears. In the rest five cases, the presence of leukocyte inclusion bodies were ambiguous. Abnormal staining of neutrophil NMMHCA was detected in all cases. In five cases with leukocyte inclusions, type I and type II NMMHCA staining were observed. In five cases without leukocyte inclusions, type II and speckled type III NMMHCA staining were detected. Mutational analysis showed that cases with type I were associated with exon 40 mutations, those with type II were associated with exon 26 and 30 mutations. Speckled type III were associated with exon 16 mutations. Thus the immunoreactivity pattern of NMMHCA correlates well with the mutational status of the MYH9 gene. In a subset of isolated macrothrombocytopenias, leukocyte inclusion bodies are merely unrecognizable on stained blood smears. Immunofluorescence analysis of neutrophil NMMHCA localization represents a clear and unambiguous alternative to conventional staining for the detection of minute leukocyte inclusions and the diagnosis of the autosomal dominant macrothrombocytopenias caused by MYH9 mutations.
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