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DIAGNOSTIC METHODS BY DNA ANALYSIS OF DRIED BLOOD SPOTS AND CLASSIFICATION OF INHERITED DISEASE BY MUTANT GENOTYPES.

Research Project

Project/Area Number 02557041
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

NARISAWA K  Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. PROF., 医学部, 教授 (90004647)

Co-Investigator(Kenkyū-buntansha) SUZUKI Y  Tohoku Univ, Sch, of Med. Dept. of Biochem. Genet. ASSIST. PROF., 医学部, 助手 (80216457)
KURE S  Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. ASSIST. PROF., 医学部, 助手 (10205221)
MATSUBARA Y  Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. ASSOC. PROF., 医学部, 助教授 (00209602)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥17,300,000 (Direct Cost: ¥17,300,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥14,700,000 (Direct Cost: ¥14,700,000)
KeywordsMOLECULAR GENETICS / GENE CLONING / GENE ANALYSIS / GENETIC DIAGNOSIS / INHERITED DISEASE / 遺伝子診断 / 遺伝子変異 / 中鎖アシルCoA脱水素酵素 / メチルマロン酸血症
Research Abstract

1. Medium chain acyl-CoA dehydrogenase(MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death. A point mutation of lysine(329)-to-glutamic acid(329)substitution in the MCAD gene was identified as the most common mutation in patients with MCAD deficiency. This mutation is responsible for about 90% of mutant MCAD alleles in Caucasians and now be detected by DNA diagnostic methods using Guthrie cards. Screening for the mutation among newborns in England, Australia, and United States of America indicates the prevalence of carriers to be 1 of 40-107, suggesting the high incidence of the mutation.
2. Nonketotic hyperglycinemia(NKH) is an autosomal recessive metabolic disorder. We have cloned and characterized a human glycine decarboxylase cDNA responsible for NKH. This clone was 3,705 bp in length and encoded 1,020 amino acids. NKH is a disorder with high incidence in northern Finland. To understand the genetic backgr … More ound of this high incidence, we examined the glycine decarboxylase in a typical case of NKH. Structural analysis of glycine decarboxylase mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser(564) to Ile(564). The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% of glycine decarboxylase gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland.
3. Phenylketonuria(PKU) is an autosomal recessive disorder caused by a deficiency of the hepatic phenylalanine hydroxylase. We have developed a simple rapid DNA screening test that allows us to analyze seven known PKU mutations in Orientals, This method is based on an allele specific PCR of the genomic DNA extracted from Guthrie cards and provides an easy method of simultaneously analyzing plural mutations. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] MATSUBARA,Y.et.al.: "Identification of a common mutation in patients with medium-chain acyl CoA dehydrogenase dcficiency." Biochem.Biophys.Res.Commun.171. 498-505 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] MATSUBARA,Y.et.al.: "Prevalence of K329E mutation in medium-chain acyl-CoA dehydrogenase gene determined from Guthrie Cards." LANCET. 338. 552-553 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KURE,S.et.al.: "Identification of a common mutation in Finnish patients with lymphoblasts." J.Clin.Invest.90. 160-164 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KURE,S.et.al.: "Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts." J.Pediatr.120. 95-98 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] ENDO,H.et.al.: "A four-nucleotide insetion at the Elα gene in a patient with pyruvate dehydrogenase deficiency." J.Inher.Metab.Dis.14. 793-799 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] TAKAHASHI,K.et.al.: "Novel phenylketonuria mutation detected by analysis of ectopically transcribed phenylalanine hydroxylasemRNA from lymphoblast." LANCET. 340. 1473 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsubara, Y. et. al.: "Identification of a common mutation in patients with medium-chain acyl CoA dehydrogenase deficiency." Biochem. Biophys. Res. Commun.171. 498-505 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsubara, Y. et. al.: "Prevalence of K329E mutation in medium-chain acyl-CoA dehydrogenase gene determined from Guthrie Cards." LANCET. 338. 552-553 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kure, S. et. al.: "Identification of a common mutation in Finnish patients with lymphoblasts." J. Clin. Invest.90. 160-164 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kure, S. et. al.: "Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts." J. Pediatr.120. 95-98 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Endo, H. et. al.: "A four-nucleotide insertion at the E1alpha gene in a patient with pyruvate dehydrogenase deficiency." J. Inher. Metab. Dis.14. 793-799

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takahashi, K. et. al.: "Novel phenylketonuria mutation detected by analysis of ectopically transcribed phenylalanine hydroxylase mRNA from lymphoblast." LANCET. 340. 1473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kure,S.et.al.: "ENZYMATIC DIAGNOSIS OF NONKETOTIC HYPER-glycinemia with lymphoblasts." J.Pediatr.120. 95-98 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsubara,Y.et.al.: "Medium-chain acyl-CoA dehydrogenase deficiency:molecular aspects." Eur.J.Pediatr.151. 154-159 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kure,S.et.al.: "Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia." J.Clin.Invest.90. 160-164 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsubara,Y.et.al.: "Dried blood spot on filter paper as a source of mRNA." Nucl.Acid.Res.20. 8- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi,K.et.al.: "Phenylketonuria-A novel mutation detected by the analysis of ectopically.transcribed phenylalanine hydroxylase mRNA from lymphoblast." LANCET. 340. 1473- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsubara,Y.,et.al.: "New Development in Fatty Acid Oxidation" A John Wiley & Sons,INC.,Publication, 10 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kure,S.: "Structural and analysis of normal and mutant mRNA encoding glysine decarboxylase: Three base deletion in mRNA causes nonketotic hyperglycinemia." Biochem.Biopys.Res.Commun.174. 1176-1182 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsubara,Y.: "Prevalence of K329E mutation in medium-chain acyl-CoA dehydrogenase gene determined from Guthrie cards." LANCET. 338. 552-553 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ohura,T.: "Genetic heterogeneity of propionic acidemia; Analysis of 15 Japanese patients." Human Genetics. 87. 41-44 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kure,S.: "Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia." J.Clin.Invest.

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsubara,Y.: "Medium-Chain acyl-CoA dehydrogenase deficiency: molecular aspects." Eur.J.Pediatr.

    • Related Report
      1991 Annual Research Report
  • [Publications] Mikami,H.: "Molecular analysis of methlmalonic acidemia."

    • Related Report
      1991 Annual Research Report
  • [Publications] MATSUBARA,Y.: "IDENTIFICATION OF A COMMON IN PATIENTS WITH MEDIUMーCHAIN ACYLーCOA DEHYDROGENASE DEFCIENCY." BIOCHEM.BIOPHYS.RES.COMMUN.171. 498-505 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] KURE,S.: "STRUCTUAL AND EXPRESSION ANALYSIS OF NORMAL AND MUTANT mRNA ENCODING GLYCINE DECARBOXYLASE:THREE BASE DELETION IN IN mRNA CAUSES NONKETOTIC HYPERGLYCINEMIA." BIOCHEM.BIOPHYS.RES.COMMUN.

    • Related Report
      1990 Annual Research Report
  • [Publications] MATSUBARA,Y.FREO__〜UENCY OF THE LISINE (329)ーTOーGLUTAMIC ACID MUTATION IN THE MEDIUMーCHAIN ACYLーCOA DEHYDROGENASE GENE AMONG^^' THE BRITISH,AUSTRALIAN,AND NORTH AMERICAN POPULATIONS.: "HUMAN GENETICS"

    • Related Report
      1990 Annual Research Report
  • [Publications] ENDO,H.: "A FOURーNUCLEOTIDE INSERTION AT THE Elα GENE IN A PATIENT WITH PYRUVATE DEHYDROGENASE DEFICIENCY." J.INHER.METAB.DIS.

    • Related Report
      1990 Annual Research Report
  • [Publications] KURE,S,NARISAWA,K.TADA,K.: "ENZYMATIC DIAGNOSIS OF NONKETOTIC HYPERGLYCINEMIA;A NOVEL ASSAY OF GLYCINE CLEACAGE SYSTEM ACTIVITY USING LYMPHOBLASTS TRANSFORMED BY EPSTEINーBARR VIRUS." J.PEDIATR.

    • Related Report
      1990 Annual Research Report
  • [Publications] OHURA,T.MIYABAYASHI,S.NARISAWA,K.TADA,K.: "GENETIC HETEROGENEITY OF PROPIONIC ACIDEMIA:ANALYSIS OF 15 JAPANESE PATIENTS." HUMAN GENEICS.

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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