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Molecular characteriztion of galactosemia type 1 : the study for gene expression system in autosomal recessive disease

Research Project

Project/Area Number 04670615
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

ISSHIKI Gen  Osaka City University Medical School Department of Pediatrics, Professor, 医学部, 教授 (80046995)

Co-Investigator(Kenkyū-buntansha) OKANO Yoshiyuki  Osaka City Univ.Med.Sch.Dept.of Ped.Assistant, 医学部, 助手 (60231213)
TANAKA Akemi  Osaka City Univ.Med.Sch.Dept.of Ped.Lecturer, 医学部, 講師 (30145776)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsGalactosemia / Inherited metabolic disease / Calactose-1-phosphate uridy, 1 transferase / Mutation / Autosomal Recessive / Gene Expression / 先天性代謝異常症
Research Abstract

Classic deficiency galactosemia is an autosomal recessive genetic disorder caused by a deficiency of galactose-1-phosphate uridyl transferase (GALT).We characterized three novel mutations of the GALT gene, and idenified N314D and R333W mutations, previously found in Caucasians from seven Japanese families with GALT deficiency.One novel missense mutation was a G to A transition in exon 8, resulting in the substitution of arginine by histidine at the codon 231 (R231H).GALT activity of the R231H mutant construct was reduced to 15% of normal controls in a COS cell expression system.The second missense mutation was a A to G transition in exon 5, resulting in substitution of methionine by valine at the codon 142 (M142V).The third was a splicing matation, an A to G transition at the 38th nucleotide in exon 3 (318A*G), resulting in a 38 bp deletion in the GALT cDNA by activating a cryptic splice acceptor site. These three mutations were not found in Caucasians.In seven Japanese families (14 alleles for classic form and one allele for Duarte variant) with GALT deficiency, R231H and 318A * G were found only on both alleles of the proband. M142V was found on two alleles with compound heterozygote in two families. N314D and R333W were found on one allele each.Q188R was prevalent in the United States but not in Japanese patients. N314D was associated with the Duarte variant in Japanese as well as in the United States.We identified the mutation in 8 of 15 alleles (53%).We speculate that the N314D GALT mutation encoding the Duarte variant arose before Asian and Caucasian people diverged and that classic galactosemia mutations arose and/or accumulated after Asian and Caucasian people diverged.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Ashino J.: "Molecular Characterization of Galactoscmia(Type1)Mutations in Japanese" Human Mntations. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岡野善行: "Pku ガラクトース血症のDNA診断" 組織培養. 20. 446-450 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岡野善行: "新内科学大系:ガラクトース代謝異常症" 中山書店, (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岡野善行: "臨床DNA診断法:ガラクトース血症" 金原出版, (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ashino, Jiro: "Molecular characterization of galactosemia (type 1) mutations in Japanese" Human Mutation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okano, Yoshiyuki: "Molecula basis of phenylketonuria and galactosemia" Tissue Culture. 20. 446-450 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okano, Yoshiyuki: "Disorders of galactose metabolism" Handbook of Internal Medicine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okano, Yoshiyuki: "Galactosemia" Clinical DNA Diagnosis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ashino J.: "Molecular Characterization of Galactosemia (Typel)Mutahons in Japanese" Human Mutations. (in Press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 岡野善行: "PKU、ガラクトース血症のDNA診断" 組織培養. 20. 446-450 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 岡野善行: "新内科学体系:ガラクトース代謝異常症" 中山書店, (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 岡野善行: "臨床DNA診断法:ガラクトース血症" 金原出版, (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ashino,Jiro: "Molecular Charactorization of two galactosemia Mutations (type1)in Orientals" American Journal of Human Genetics. 53(Abstract). 887 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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