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Genetic analysis in families with amyotrophic lateral sclerosis

Research Project

Project/Area Number 11470144
Research Category

Grant-in-Aid for Scientific Research (B).

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

Principal Investigator

ITOYAMA Yasuto  Tohoku University, School of Medicine, Department of Neurology, Professor, 大学院・医学系研究科, 教授 (30136428)

Co-Investigator(Kenkyū-buntansha) AOKI Masashi  Tohoku University, School of Medicine, Department of Neurology, Research Associa, 医学部・附属病院, 助手 (70302148)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsAutosomal dominant / amyotrophic lateral sclerosis / linkage analysis / familial / motor neuron / motor neuron disease
Research Abstract

Amyotrophic lateral screlosis (ALS) is a fatal neurodegenerative disease caused by selective death of motor neurons. Pathological studies of postmortem ALS patients revealed motor neuron loss in the anterior horn of the spinal cord, the nucleus of brainstem and the cortex. Approximately 10% of cases of ALS are inherited, usually as an autosomal dominant trait. Mutations of the cytosolic cupper-zinc superoxide dismutase (Cu/Zn SOD) gene were detected in about 25% of patients with familial ALS and until now more than 70 different mutations are known. In this study, we carry out a linkage analysis using a large Japanese family with ALS to identify loci that contain genes whose defects cause ALS.We did not detect any genetic linkage to the known locus of motor neuron diseases and now going on a genome-wide linkage analysis. In addition, we identified a novel missense mutation of the Cu/Zn SOD gene (Leu126Ser) in a Japanese family with ALS that included a patient with the homozygous mutation. The expression of the Cu/Zn SOD polypeptide in erythrocytes was markedly reduced in the case with the homozygous mutation compared to those with the heterozygous mutation. We speculated that this reduction of the mutant Cu/Zn SOD molecule may be related to the severe clinical phenotype of the case.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Tsuchiya K et al.: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusion bodies : a clinical, genetic and pathological study."Clin Neuropath. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Trotti D et al.: "Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity."J Biol Chem. 276. 576-582 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Onodera Y et al.: "High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan"J Neurol Sci. 178. 155-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuchiya K, Matsunaga T, Aoki M, Haga C, Ooe K, Abe K, Ikeda K and Nakano I: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusion bodies : a clinical, genetic and pathological study."Clin Neuropath. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Trotti D, Aoki M, Pasinelli P, Berger UV, Danbolt NC, Brown RH Jr and Hediger MA: "Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity."J Biol Chem. 276. 576-582 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Onodera Y, Aoki M, Tsuda T, Kato H, Nagata T, Kameya T, Abe K and Itoyama Y.: "High preverance of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan"J Neurol Sci. 178. 155-160 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary

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Published: 1999-04-01   Modified: 2016-04-21  

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