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Propionic acidemia : Molecular analysis of beta subnit deficient Japanese petients

Research Project

Project/Area Number 04670575
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

OHURA Toshihiro  Tohoku Univ., Dept. of Pediatrics, School of Medicine, Assistant Professor, 医学部・附属病院・小児科, 講師 (10176828)

Co-Investigator(Kenkyū-buntansha) KURE Shigeo  Tohoku Univ., Dept. of Biochemical Genetics, School of Medicine, Instructor, 医学部・病態代謝学, 助手 (70211191)
呉 繁夫  東北大学, 医学部, 助手 (10205221)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsPropionic Acidemia / Propionyl CoA Ccrboxylase / Exon skipping
Research Abstract

Propionic acidemia is a recessively inherited disorder of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase (PCC) activity. Enxyme deficiency can result from mutations in either the alpha or the beta subunit. The human beta-PCC cDNA was sequenced in full and shown to encode a pre-beta subunit of 539 amino acids. Polymerase chain reaction amplification and sequencing of betaPCC cDNA from five beta-subunit deficient Japanese patients (cell no.83,187,212,276,338) revealed two missense mutations (C1283T, C493T), one nonsense mutation (C1495T) and two splicing mutations. The allele frequency of the C1283T mutation was 50% (5/10) in this study, and this mutation was not detected in 50 normal Japanese subjects. This suggests that the C1283T mutation causes disease, and may be a common mutation in Japanese propionic acidemia patients. Two deletions were found in the coding region of the beta-PCC cDNA.One is a 57-bp in-frame deletion between nucleothides 373 and 429, resulting in the deletion of 19 amino acids in the coding sequence in patient 187. Analysis of the genomic DNA from 187 revealed a 4-bp deletion from bp+3 to bp+6 of the downstream intron adjacent to the deleted exon. This deletion disrupted the consensus 5' splice signal (GTAAGT->GTGTTT) and led to exon skipping. The second deletion is a 101-bp deletion between nucleotides 1199 and 1299 in patient 338, which resulted in a frame shift and a stop codon in the new frame. Similar analysis of the genomic DNA from 338 revealed an 8-bp deletion from bp+3 to bp+10 of the donor splice site of the intron. This deletion also disrupted the consensus 5' splice signal (GTGAGG->GTCATG) and led to exon skipping.

Report

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

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 大浦 敏博: "プロピオン酸血症" 臨床検査. 36. 233 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 大浦 敏博: "日本人プロピオン酸血症患者(β鎖欠損)の遺伝子解析" 日本人先天代謝異常学会雑誌. 10(発表予定). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jahara J.,et al.: "Three independent mutation in the same exon of the PCCB gene:Differences between Cancasians and Japanese propionic acidemia." Journal of Inherited Metabolic Disease. 16. 353-360 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohura J.,et al.: "Propionic acidemia:Sequence analysis of mutant mRNAs from Japanese β subunit deficient patients." Journal of Inherited Metabolic Disease. 16. 863-867 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohura J.,et al.: "The molucular defect in propionic acidemia:exon skipping caused by an 8-bp deletion from an intron in the PCCB allele." Human genetics. 92. 397-402 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tahara T.et al: "Three independent mutations in the same exon of the PCCB gene : Differences between Caucasians and Japanese propionic acidemia" J.Inher. Metab. Dis.Vo ; .16. 353-360 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohura T.et al: "Propionic acidemia : Sequence analysis of mutant mRNAs from Japanese beta subunit deficient patients" J.Inher. Metab. Dis.Vo ; .16. 863-867 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohura T.et al: "The molecular defect in propionic acidemia : Exon skipping caused by on 8-bp deletion from an intron in the PCC B allele" Hum. Genet.Vol.92. 397-402 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 大浦 敏博: "日本人プロピオン酸血症患者(β鎖欠損)の遺伝子解析" 日本先天代謝異常学会雑誌. 10(発表予定). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jahara J.,et al.: "Three independent mutations in the same exon of the PCCB gene:Differences between Caucasians and Japanese propionic acidemia." J.Inher.Metab.Dis.16. 353-360 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohura J.,et al.: "Propionic acidemia:Sequence analysis of mutant mRNAs from Japanese β subunit deficient patients." J.Inher.Metab.Dis. 16. 863-867 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohura J.,et al.: "The molecular defect in propionic acidemia:exon skipping eaused by on 8-bp deletion from on citron in the PCCB allele." Hum.Genet.92. 397-402 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大浦 敏博 他: "日本人プロピオン酸血症患者(β鎖欠損)の遺伝子変異の検討" 日本先天代謝異常学会雑誌. 8. 109- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] OHURA,T.et al: "Propionic acidemia:Sequence analysis of mutant mRNAs from Japanese β subunit-deficient patients." Journal of Inherited Metabolic Disease. 16. (1993)

    • Related Report
      1992 Annual Research Report

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

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