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2006 Fiscal Year Final Research Report Summary

Comprehensive mutational screening of genes maintaining the glycine concentrations in the central nervous system

Research Project

Project/Area Number 17591067
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

KURE Shigeo  Tohoku-University Graduate School of Medicine, Associate professor, 大学院医学系研究科, 助教授 (10205221)

Co-Investigator(Kenkyū-buntansha) OHURA Toshihiro  Tohoku University, Graduate School of Medicine, Associate professor, 大学院医学系研究科, 助教授 (10176828)
Project Period (FY) 2005 – 2006
Keywordshyperglycinemia / GLDC / AMT / GCSH / neonatal seizures / cerebrospinal fluids / gene analysis / mutation spectrum
Research Abstract

We have screened 120 families with elevated glycine concentration in plasma and/or cerebrospinal fluids. By the previous screening of GLDC and AMT genes, we identified the causative mutations in 70% of affected families. The purpose of this study is to perform the mutational screening of other candidate gene in the rest of the 35 families. As the candidate genes, which-affect the extracellular glycine concentrations we selected five genes, the GCSH, DLD, LPT, GLYT1, and GLYT2 genes. The GLDC, AMT, and DLD genes encode enzymes which involved in the glycine metabolism while GLYT1 and GLYT2 genes encode specific transporters of glycine. In the GCSH gene, we have identified a base change at the splicing acceptor consensus sequence, AT, in intron 4. No GCSH mutation was detected in other cases. The AT was substituted into GT, which is supposed to abolish the splicing function of this intron. The patients was given a diagnosis as having transient hyperglycinemia. The other mutation identified was missense mutation in LPT gene, which resulted in amino acid substitution form arginine to glycine. The arginine residue is highly conserved among the other spices, suggesting the evolutional importance. No other mutation have been detected in this series of the mutational screening. We concluded that hyperglycinemia can be caused by the other genes than GLDC or AMT.

  • Research Products

    (12 results)

All 2007 2006

All Journal Article (12 results)

  • [Journal Article] Genomic deletion within GLDC is a major cause of nonketotic hyperglycinemia2007

    • Author(s)
      Kanno J
    • Journal Title

      J Med Genet (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A direct correlation between ischemic injury and extracellular glycine concentration in mice with altered activity of glycine cleavage multi-enzyme system2007

    • Author(s)
      Oda M
    • Journal Title

      Stroke (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genomic deletion within GLDC is a major cause of nonketotic hyperglycinemia.2007

    • Author(s)
      Kanno J et al.
    • Journal Title

      J Med Genet (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ischemia-induce brain damage depends on the glycine cleavage system via extracellular glycine concentration.2007

    • Author(s)
      Oda M, et al.
    • Journal Title

      Stroke (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prospective treatment from birth of nonketotic hyperglycinemia (NKH) due to a novel GLDC missense mutation.2006

    • Author(s)
      Korman S et al.
    • Journal Title

      Ann Neurol 59

      Pages: 411-415

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia (glycine encephalopathy)2006

    • Author(s)
      Kure S et al.
    • Journal Title

      Hum Mutat 27

      Pages: 343-352

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Rapid and non-invasive diagnosis of glycine encephalopathy by 13C-glycine breath test2006

    • Author(s)
      Kure S et al.
    • Journal Title

      Ann Neurol 59

      Pages: 862-867

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Non ketotic hyperglycinemia associated with primary pulmonary hypertension and acylglycinuria in three families2006

    • Author(s)
      Del Toro M
    • Journal Title

      Ann Neurol 60

      Pages: 148-152

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prospective treatment from birth of nonketotic hyperglycinemia (NKH) due to a novel GLDC missense mutation.2006

    • Author(s)
      Korman et al.
    • Journal Title

      Ann Neurol 59

      Pages: 411-415

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia (glycine encephalopathy).2006

    • Author(s)
      Kure et al.
    • Journal Title

      Hum Mutat 27

      Pages: 343-352

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rapid and non-invasive diagnosis of glycine encephalopathy by ^<13>C-glycine breath test.2006

    • Author(s)
      Kure S et al.
    • Journal Title

      Ann Neurol. 59

      Pages: 862-867

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Non ketotic hyperglycinemia associated with primary pulmonary hypertension and acylglycinuria in three families.2006

    • Author(s)
      Del Toro M, et al.
    • Journal Title

      Ann Neurol 60

      Pages: 148-152

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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