| Project/Area Number |
18390296
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
MATSUBARA Yoichi Tohoku University, Tohoku University School of Medicine, Professor (00209602)
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| Co-Investigator(Kenkyū-buntansha) |
KURE Shigeo Tohoku University School of Medicine, 大学院・医学系研究科, Associate Professor (10205221)
AOKI Yoko Tohoku University School of Medicine, 大学院・医学系研究科, Assistant Professor (80332500)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,080,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2006: ¥11,100,000 (Direct Cost: ¥11,100,000)
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| Keywords | Congenital anomaly syndrome / Noonan syndrome / Costello syndrome / CFC syndrome / signal transduction / genetic mutation / oncogene |
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| Research Abstract |
We have been searching for genetic abnormalities in multiple congenital anomalies/mental retardation syndromes. Recently we identified mutations in the Ras/MAPK signaling pathways among Noonan-related syndromes, namely Costello syndrome and cardiofaciocutaenous (CFC) syndrome. The purpose of the current study is to identify novel disease-causing genes related to various signal transduction pathways, to establish genetic testing protocols, and to perform functional studies to better understand the pathogenesis of these disorders. At first, we collected DNA samples and cell cultures from patients with Noonan syndrome, Costello syndrome, CFC syndrome and patients with similar clinical pictures. We performed comprehensive mutation analysis of the previously reported disease-causing genes and reported the results in a review in Human Mutation (Published Online: May 9 2008). Candidate gene analysis revealed mutations in novel genes. Functional studies of the identified mutations were performed to characterize their effects on the signaling pathway. We also started to create transgenic mice harboring mutated HRAS gene as a disease model for Costello syndrome.
The entire study was approved by the Ethics Committee of Tohoku University School of Medicine and the genetic analysis was done according to the relevant guidelines.
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