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Molecular Basis of Charcot-Marie-Tooth Disease

Research Project

Project/Area Number 14570718
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAYASAKA Kiyoshi  Yamagata University, School of Medicine, Professor, 医学部, 教授 (20142961)

Co-Investigator(Kenkyū-buntansha) KIMURA Toshiyuki  Yamagata University, University Hospital, Assistant professor, 医学部附属病院, 助手 (90292432)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHereditary neurophaties / Charcot-Marie-Tooth / sodium channel / denaturing high performance liquid chromatography / Nav 1.6 / 17p11.2遺伝子重複 / PMP22 / Po / Cx32 / EGR2SCN8A
Research Abstract

Charcot-Marie-Tooth disease (CMT) is a most common hereditary neuropathy. CMT type 1 (CMT1), the major form of the disease, is a genetically heterogeneous disease and many responsible genes have been identified. However, disease-causing mutations have not been identified in many Japanese patients. We tried to establish the reliable and easy diagnostic method to make clear the molecular basis of Japanese patients. We also studied physiological properties of Nav 1.6 channel, which plays a significant role for signal transduction in the peripheral nervous system.
We studied 143 patients with CMT1 and initially identified the CMT1A duplication in 40 patients. As for the patients without the CMT1A duplication, we screened the mutations of PMP22, Po, Cx32, EGR2, LITAF, GDAP1, MTMR2 and PRX using denaturing gradient gel electrophoresis (DGGE) and denaturing high performance liquid chromatography (DHPLC). We identified 7 patients with PMP22 mutations, 16 patients with Po mutations, 13 patients with Cx32 mutations, 1 patient with EGR2 mutation, 1 patient with MTMR2 and 3 patients with PRX mutations. Compared with the data from foreign countries, the patients due to CMT1A duplication were few and many patients (44%) were not identified their etiologies. Further study is needed to clarify the molecular basis of Japanese patients.
We previously isolated cDNA of Nav 1.6 channel and examined biophysical properties of Nav 1.6 in heterologous expression cell systems using patch clamp method. We observed large persistent current of Nav 1.6 Channel in tsA201 cells however, the persistent current was significantly reduced by the co-expression with ankyrin G. It suggested that modulation by ankyrin G may underlie site-dependant electrophysiological Characteristics of Nav 106 channels.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Numakura C et al.: "Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease : DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations."Hum Mutat.. 20. 392-398 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiihara T et al.: "Microcephaly, cerebellar atrophy and focal segmental glomerulosclerosis in two brothers : A possible mild form of Galloway-Mowat syndrome."J Child Neurol.. 18. 147-149 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori N et al.: "Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32) : a clinicopathological study of 205 Japanese patients."Brain.. 126(Pt1). 134-151 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numakura C et al.: "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1"J Neurol Sci. 210. 61-64 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurihara S et al.: "Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation"J Neurol Neurosurg Psych. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kijima K et al.: "Periaxin mutation causes early onset but slow progressive Charcot-Marie-Tooth disease"J Hum Genet. In press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numakura C et al.: "Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease : DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations."Hum Mutat.. 20. 392-398 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] SHiihara T et al.: "Fluctuation of computed tomographic finding in white matter in Alexander's disease."J.Child Nrurol.. 17. 227-230 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] SHiihara T et al.: "Progressive sliding hiatal hernia as a complication of Menkes' syndrome."J.Child Neurol.. 17. 401-402 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanai M et al.: "Congenital central hypoventilation syndrome : a novel mutation of the RET gene in an isolated case."Tohoku J Exp Med.. 196. 241-246 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsunaga A et al.: "Association of the uteroglobin gene polymorphism with IgA nephropathy."Am J Kid Dis. 39. 36-41 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] SHiihara T et al.: "Microcephaly, cerebellar atrophy and focal segmental glomerulosclerosis in two brothers : A possible mild form of Galloway-Mowat syndrome."J Child Nerol.. 18. 147-149 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori N et al.: "Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients."Brain.. 126(Pt 1). 134-151 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numakura C et al.: "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1."J Neurol Sci. 210. 61-64 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanai M et al.: "Neonatal hyperbilirubinemia in Japanese : Analysis of the heme oxygenase-1 gene and fetal hermoglobin composition in cord blood."Pediatr Res.. 54. 1-8 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki A et al.: "Molecular analysis of congenital central hypoventilation syndrome."Hum Genet. 114. 22-26 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurihara S et al.: "Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation."J Neurol Neurosurg Psych. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kijima K et al.: "Periaxim mutation causes early onset but slow progressive Charcot-Marie-Tooth"J Hum Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numakura C et al.: "Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease : DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations"Hum Mutat.. 20. 392-398 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiihara T et al.: "Microcephaly, cerebellar atrophy and focal segmental glomerulosclerosis in two brothers : A possible mild form of Galloway-Mowat syndrome"J Child Neurol.. 18. 147-149 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori N et al.: "Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32) : a clinicopathological study of 205 Japanese patients"Brain. 126(Pt1). 134-151 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Numakura C et al.: "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1"J Neurol Sci. 210. 61-64 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurihara S et al.: "Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation"J Neurol Neurosurg Psych. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Chikahiko N. et al.: "Molecular Analysis in Japanese Patients With Charcot-Marie-Tooth Disease : DGGE Analysis for PMP22, MPZ, and Cx32/GJB1 Mutations"Human Mutation. 20. 392-398 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naoki Hattori. et al.: "Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, NPZ and Cx32) : a clinicopathological study of 205 Japanese Patients"Brain. 126. 134-151 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 種市 尋宙他: "ビンクリスチン投与により顕性化したCharcot-Marie-Tooth病1A型の1例"日本小児血液学会雑誌. 17. 34-37 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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