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2003 Fiscal Year Final Research Report Summary

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
KeywordsHereditary neurophaties / Charcot-Marie-Tooth / sodium channel / denaturing high performance liquid chromatography / Nav 1.6
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.

  • Research Products

    (18 results)

All Other

All Publications (18 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2005-04-19  

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