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Recurrent deletion in glycine decarboxylase gene and nonketotic hyperglycinemia Medical genetics, Research

Research Project

Project/Area Number 10672134
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

KURE Shigeo  Pediatrics, Tohoku University Associate professor, 大学院・医学系研究科, 助手 (10205221)

Co-Investigator(Kenkyū-buntansha) OHURA Toshihiro  Pediatrics, Tohoku University Associate professor, 大学院・医学系研究科, 助教授 (10176828)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsglycine decarboxylase / Alu repeats / non-ketotic hyperglycinemia / deletion / homologous recombination / glycine decarboxylase / Nonketotic hyperglycinemia / Homologous recombination / ghycime decarboxylase / nonkefotic hyperglycimemia / homologous recommbination
Research Abstract

Mutations in glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We determined the structures of GLDC and its pseudogene (psiGLDC) and studied their expression in molecular analysis of NKH. The GLDC gene spanned a least 135 kb and consisted of 25 exons. All donor and acceptor sites adhered to the canonical GT-AG rule except for the donor site of intron 21, where a variant form GC was used instead of GT. The transcription initiation site was assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The psiGLDC gene had no intron and shared 97.5% homology with the coding region of functional GLDC, suggesting that psiGLDC ia a processed pseudogene that arose from the GLDC transcript about 4 to 8 million years ago. RNA blotting analysis revealed that GLDC is expressed in human liver, kidney, brain and placenta. We then examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1 to 3 of the functional GLDC gene from this patient were not amplified by PCR, whereas those from control subjects were amplified. These results suggest a large homozygous deletion (at least 30 kb) in the patient. We then devise a semi-quantitative PCR to estimate the number of GLDC alleles using psiGLDC as an internal control, and confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and psiGLDC should facilitate the molecular analysis of NKH.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Mikami H,et al.: "Molecular analysis of Japanese patients with・・"J. Hum. Genet.. 44. 35-39 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagasaki Y,et al.: "Reversal of hypopigmentation in phenylketonuria mice・・"Pediatric Res.. 45. 465-473 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S,et al.: "Prenatal diagnosis of nonketotic hyperglycinemia・・"Prenat. Diagn.. 19. 717-720 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jackson AH,et al.: "Atypical nonketotic hyperglycinemia with normal・・"J. Child Neurol.. 14. 464-467 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S,et al.: "Tetrahydrobiopterin-responsive phenylalanine hydroxylase・・"J. Pediatr. 135. 375-378 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hou DC,et al.: "Molecular analysis of glycogen storage disease・・"Am. J. Med. Genet.. 86. 253-257 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S,et al.: "Apo A・I Miyagi(947delA) : a novel deletion in the・・"Hum. Mutation. 13. 341-341 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Von der Knaap,et al.: "A biochemical marker for a leuko encephalopathy・・"J. Child Neurol.. 14. 728-731 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kudo T,et al.: "New common mutation in the Connexin 26・・"Am. J. Med. Genet.. 90. 141-145 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii K,et al.: "Mutation detection by taqMan-allele specific・・"Hum. Mutation. 15. 189-196 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takayanagi M,et al.: "Human glycine decarboxylase(GLDC) gene and・・"Hum. Genet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mikami, H, Ogasawara M, Matsubara Y, Kikuchi M, Miyabayashi S, Kure S, Narisawa K.: "Molecular analysis of Japanese patients with methylmalonyl CoA mutase deficiency."J Hum Genet. 44. 35-39 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagasaki Y, Matsubara Y, Takano H, Fujii K, Senoo M, Akanuma J, Takahasi K, Kure S, Hara M, Kanagane Y, Saito I, Narisawa K.: "Reversal of hypopigmentation in phenylketonuria mice by adenovirus-mediated gene transfer."Pediatric Res. 45. 465-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S, Rolland MO, Leistri J, Mandel H, Sakata Y, Tada K, Matsubara Y, Narisawa K.: "Prenatal diagnosis of nonketotic hypergylcinemia: Enzymatic diagnosis in 28 families and DNA diagnosis by detecting Finnish and Israeli-Arab prevalent mutations."Prenat Diagn. 19. 717-720 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jackson AH, Applegarth DA, Toone JR, Kure S, Levy HL.: "Atypical nonketotic hyperglycinemia with normal CSF : plasam glycine ratio."J Child Neurol. 14. 464-467 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S, Hou DC, Ohura T, Iwamoto H, Suzuki S, Sugiyama N, Sakamoto O, Fujii K, Mtsubara Y, Narisawa K.: "Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency."J Pediatr. 135. 375-378 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hou DC, Kure S, Suzuki Y, Hasegawa Y, Hara Y, Inoue T, Kida Y, Matsubara Y, Narisawa K.: "Molecular analysis of glycogen storage disease type Ib:Structural and mutational analysis of the gene encoding microsomal glucose-6-phosphate translocase."Am J Med Genet. 86. 253-257 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kure S, Hou Dc, Satoh M, Matsubara Y, Narisawa K.: "Apo A-Imiyagi(947delA): a novel deletion in the apolipoprotein A-I gene associated with familial hypoalphalipoproteinemia."Hum Mutation. 13. 341 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] von der Knaap MS, Wevers RA, Kure S, Gabreels FJM, Verhoeven NM, van Raay-Selten B, Jaaken J.: "Increased CSF glycine; A biochemical marker for a leukoencephalopathy with vanishing white matter."J Child Neurol. 14. 728-31 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kudo T, Ikeda K, Kure S, Matsubara Y, Oshima, T, Kawase T, Narisawa K, Takasaka T.: "New common mutation in the Connexin 26 gene (GJB2) in childhood deafness in the Japanese population."Am J Med Genet 2000. 90. 141-145 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii K, Matsubara Y, Akanuma J, Takahashi K, Kure S, Suzuki Y, Imaizumi M, Iinuma K, Sakatsme O, Rinaldo P, Kuniaki Narisawa.: "Mutation detection by TaqMan-allele specific amplification: its application to the molecular diagnosis of glycogen storage disease type Ia and medium-chain acyl-CoA dehydrogenase deficiency."Hum Mutaion. 15. 189-196 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takayanagi M, Kure S, Tada K, Sakata Y, Kurihara Y, Ohya Y, Kajita M, Tada K, Matsubara Y, Narisawa K.: "Human glycine decarboxylase (GLCD) gene and its processed type pseudogene: Structures, expression, and identification of a large deletion in a family with nonketotic hyperglycinemia."Human Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mikami H.et al.: "Molecular analysis of methylmalonyl-CoA mutase deficiency : identification of three missense mutation in mut patients"Journal of Human Genetics. 44. 35-39 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagasaki Y.et al.: "Reversal of hypopitmentation in phynylketonuria mice by adenovirus-mediated gene transfer"Pediatric Research. 45,4. 465-473 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kure S.et al.: "Prenatal diagnosis of non-ketotic hyperglycinemia : enzymatic diagnosis in 28 families and DNA diagnosis detecting prevalent Finissh and Israel-Arab mutations"Prenatal Diagnosis. 19. 717-720 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jackson AH.et al.: "A typical monketotic hyperglycinemia with normal CSF : plasam glycine ratio"Journal of Child Neurology. 14. 464-467 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kure S.et al.: "Tetrahydrobiopterine-responsive phenylalanine hydrosylase deficiency"Journal of Pediatrics. 135. 357-378 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hou D.et al.: "Glycogen storage disease type Ib : structural and mutation analysis of the microsomal glucose-6-phosphate transporter gene"American Journal of Human Genetics. 86,3. 254-257 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kure S.et al.: "Apo A-I Miyagi(947delA) : a novel deletion in the apolipoprotein A-I gene associated with familial hypoalphalipoproteinemia"Human Mutation. 13. 341 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Von der Knaap et al.: "A biochemical marker for a leukoencephalopathy with vanishing white matter"Journal of Child Neurology. 14. 728-731 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kudo T.et al.: "New common mutation in the Connexine 26 gene in childhood deafness in the Japanese population"American Journal of Medical Genetics. 90. 141-145 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujii K.et al.: "Mutation detection by TaqMan-allele specific amplification : Application to molecular diagnosis of glycogen storage disease type Ia and medium-chain acyl-CoA dehydrogenase deficiency"Human Mutation. 15,2. 189-196 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takayanagi M.et al.: "Human glycine decarboxylase (GLDC) gene and its processed type pseudogene"Human Genetics. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kure S,et.al.: "Amissense mutation (His42Arg) in the T-protein gene from・・・" Human Genetics. 102. 430-434 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kure S,et.al.: "Mutation and polymorphic marker analyses of 65K-and 67K-" Journal of Human Genetics. 43. 128-131 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kure S,at.al.: "A subtype of pyridoxime dependent epilepsy with・・・" J Inher Metabol Dis. 21. 431-432 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kure S,et.al.: "A one-base deletion and a missense mutation (D276H)" J Hum Gemet. 43. 135-137 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kure S,et.al.: "Molecular analysis of glycogen storage disease type Ib" Biochem Biophysis Res Commun. 248. 426-431 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mikami H,et.al.: "Molecular analysis of Japanese patients with・・・" J Hum Genetics. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinka T,et.al.: "Assignment of gldc encoding glycine decarboxy lase・・・" Cytogenet Cell Genet. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Jackson Alt,et al.: "Atypical nonketotic hyperglycinemia with normal CSF" J Child Neurol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagasaki Y,et.al.: "Reversal of hypopigmentation in phemylhetonuria mice by" Pediatr Res. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Kure S,et al: "Apo A-I (Miyagi) (947delA) : a novel deletion in the apdipoprotein" Human Mutation. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] van der Knaap,et al: "A biochemical marker for a leukocncephalophthy with" J Child Neurol. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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