2014 Fiscal Year Final Research Report
Genetic analysis of a new syndrome with aberrant JAK2 splicing
| Project/Area Number |
23591550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Takashi 杏林大学, 医学部, 教授 (00191768)
OHTSUKA Kouki 杏林大学, 医学部, 助教 (70439165)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Keywords | JAK2 / スプライシング異常 / 骨髄増殖性腫瘍 / GATA1 |
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| Outline of Final Research Achievements |
We found a JAK2 splicing mutation in an infant and a fetus presenting with myeloproliferative neoplasm and genital anomalies. No enhancement of phosphorylation of downstream signal molecules was observed in cell lines with this JAK2 mutation. Transgenic mice with this aberrant JAK2 did not develop hematopoietic abnormalities or genital anomalies. To explore the underlying mechanism causing these clinical features and aberrant JAK2 splicing, we performed exome analysis for these patients and their parents and siblings. We identified G221D mutation of GATA1 gene located on X chromosome in these patients and their mother, suggesting that GATA1 mutation is associated with the hematopoietic abnormalities in these patients. In addition, we found mutations in DGKK gene, which is reported to be related to hypospadias, suggesting that DGKK mutation is associated with the genital anomalies in these patients.
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| Free Research Field |
小児血液腫瘍学
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