| Project/Area Number |
13670779
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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 |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
KURE Shigeo Tohoku University School of Medicine, Department of Medical Genetics, Associate Professor, 大学院・医学系研究科, 助教授 (10205221)
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| Co-Investigator(Kenkyū-buntansha) |
OHURA Toshihiro Tohoku University School of Medicine, Department of Pediatrics, Associate Professor, 大学院・医学系研究科, 助教授 (10176828)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | hyperglycinemia / glycine cleavage system / disturbances in central nervous system / GCSH gene / transient hyperglycinemia / gene mutation / splicing error / グリシン開裂素系 / グリシン脱炭酸素遺伝子 / 遺伝子多型マーカー / イスラエル / 大家族 / 常染色体劣性遺伝 / 染色体マッピング |
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| Research Abstract |
Transient neonatal hyperglycinemia (TNH) is clinically or biochemically indistinguishable from nonketotic hyperglycinemia at onset. In the case of TNH the elevated plasma and CFS glycine levels are normalized within 2-8 weeks. To elucidate the pathogenesis of TNH and idntification of a novel gene for hyperglycinemia we studied three patients by screening mutations in the genes that encode components of the glycine cleavage system (GCS). The GCS is a mitochondrial multi-enzyme system that consists of four individual components; P-protein, glycine decarboxylase; T-protein, aminomethyltransferase; H-protein, hydrogen carrier protein; L-protein, dihydrolipoamide dehydrogenase. P, T, H, and L-proteins were encoded by GLDC, AMT, GCSH, and GCSL genes, respectively. Several NKH-causing mutations have been identified in GLDC and AMT. No mutations have been identified in GCSH to date. Heterozygous mutations were identified in all of the three patients suggesting that TNH develops in some heterozygous carriers for nonketotic hyperglycinemia. We identified a splicing mutation of GCSH gene for the first time, indicating that GCSH gene is responsible for hyperglycinemia.
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