• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular Analysis of Galactosemia

Research Project

Project/Area Number 07670889
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOsaka city University Medical School

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) OKANO Yoshiyuki  Osaka City University Medical School, Associate Professor, 医学部, 講師 (60231213)
TANAKA Akemi  Osaka City University Medical School, Assosiate Professor, 医学部, 講師 (30145776)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsgalactosemia / galactokinase / galactose 1-phosphate uridyltransferase / mutation / phenotype / inherited Metabolic disease / 遺伝子解析 / ガラクト・ウリジル・トランスフェラーゼ / 常染色性劣性遺伝
Research Abstract

Galactosemia (Type 1) is an autosomal recessive genetic disorder due to galactose 1-phosphate uridyltransferase (GALT) deficiency. We characterzed 13 mutations of GALT gene in 13 patients from 11 families by PCR amplification, denaturing gradient gel electorophoresis, and direct sequence analysis. We found 9 missense mutations (N97S,M142V,G179D,A199T,W249R,N314D,P325L,R333Q,R333W), two deletions (852T-del, 977C-del), a nonsense mutation (W249X), and a splicing mutations (IVS4nt+1). These 10 mutations except for N314D and P325L,R333W have not been found in Caucasians. Duarte variant with the N314D mutation in Japanese was associated with Sac I (-) in RFLP analysis as well as in Caucasians. We suggest the galactosemic mutation may have occured after racial divergence between Caucasians and Asians, and the N314D mutation may have occured before racial divergence. The GALT activities of all mutants GALT constructs in the COS cell expression system were reduced to 1%-35% of normal constructs, and were correlated with biochemical and clinical phenotypes. Genotyping of the GALT gene can characterize patiens with GALT dificiency, and can be useful for clinical use.
Galactokinase (GALK) is caused by the deficiency of galactokinase. We have independently characterized the sequence of the human GALK gene, which consisted of 8 exons spanning 7.3kb. We have identified five novel mutations in seven Japanese patients with GALK deficiency, which were three missense mutations (R256W,T344M and G349S) and two deletions (405Del-G,505Del-2). These missense mutations led to a drasticredution in GALK activity when indiviual mutant cDNAs were expressed in a mammalian cell system, The results indicate that these missense mutations were the cause of GALK deficiency. These mutations in Japanese have not yet been found in Caucasians.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Ashino J.: "Molecular Characterization of Galactosemia(Type 1)Mutations in Japanese." Hum.Mut.6・1. 36-43 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.,: "Newborn mass screening and molecular genetics of phenylketonuria in east Asians." Southeast Asian J.Tropical Med.and Pub.Health. 26・Supp 1. 123-129 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 廣川 秀徹: "ガラクトース血症I型の遺伝子型からみた臨床像への手がかり" 特殊ミルク情報. 33・1. 38-40 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 岡野 善行: "ガラクトース-1ーリン酸ウリジルトランスフェラーゼ欠損症" Molecular Medicine. 32. 32-33 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 岡野 善行: "ガラクトキナーゼ欠損症、UDP-ガラクトース-4-エピメラーゼ欠損症" Molecular Medicine. 32. 34-35 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 岡野 善行: "ガラクトース代謝異常症:最新内科学体系 8糖質・アミノ酸代謝異常" 中山書店, 8 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 岡野 善行: "ガラクトース血症:小児科学" 医学書院, 4 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ashino J.: "Molecular Characterzation of Galactosemia (Type 1) Mutations in Japanese." Hum.Mutat. 6-1. 36-43 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.: "Newborn mass screening and molecular genetics of phenylketonuria in East Asians." Southeast Asian J.Tropical Med.and Pub.Health. 26・Supp 1. 123-129 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirokawa H.: "Molecular characterization of galactosemia." Bulletin on Special Formula. 33-1. 38-40 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.: "Galactose 1-phosphate uridyltransferase deficiency." Molecular Medicine. 32. 32-33 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.: "Galactokinase deficiency.and UDP-galactose 4'epimerase deficiency." Molecular Medicine. 32. 34-35 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.: Nakayama shoten.(Tokyo). Galactosemia.in Integrated Handbook of Internal Medicine 8.(Imura H.et al eds.), 148-156 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okano Y.: Igakushoinn.(Tokyo). Galactosemia.in Text book of Pediatrics. (Shiraki K.Maekawa K eds.), 320-322 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 廣川秀徹、岡野善行: "ガラクトース血症I型の遺伝子型からみた臨床像への手がかり" 特殊ミルク情報. 33・1. 38-40 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 岡野善行: "ガラクトース血症:小児科学" 医学書院, 4 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ashino,J.: "Molecular Characterization of Galactosemia(Type 1)Mutations in Japanese" Human Mutation. 6. 36-43 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡野 善行: "ガラクトース-1ーリン酸ウリジルトランスフェラーゼ欠損症(遺伝子病マニュアル)" Molecular Medecine. 32. 32-33 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡野 善行: "ガラクトキナーゼ欠損症.UDP-ガラクトース-4エピキラーゼ欠損症(遺伝子病マニュアル)" Molecular Medecine. 32. 34-35 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡野 善行: "臨床DNA診断法" 金原出版, 3 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡野 善行: "最新内科学体系" 中山書店, 8 (1995)

    • Related Report
      1995 Annual Research Report

URL: 

Published: 1995-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi