1999 Fiscal Year Annual Research Report

グリシン脱炭酸酵素遺伝子の高頻度欠失領域と高グリシン血症の病型

Research Project

Project/Area Number	10672134
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	呉繁夫東北大学, 大学院・医学系研究科, 助手 (10205221)
Co-Investigator(Kenkyū-buntansha)	大浦敏博東北大学, 大学院・医学系研究科, 助教授 (10176828)
Keywords	glycine decarboxylase / Alu repeats / Nonketotic hyperglycinemia / deletion / Homologous recombination
Research Abstract	一過性非ケトーシス型高グリシン血症(transient nonketotic hyperglycinemia:NKH)患者と重症型NKH患者の両グリシン脱炭酸酵素遺伝子の中に、第1エクソン上流から第3イントロンの大部分を含む大きな欠失(50kb以上)が存在することを見いだした。この欠失は、様々な人種で共通に認められ日本人、フィンランド、白人患者の変異アレルのそれぞれ25%、23%、20%を占める。更にこの欠失を持つ患者を詳細に検討した結果、一過性高グリシン血症患者のGLDC遺伝子には他に遺伝子変異はなく、欠失のあるアレルのもう一方は正常アレルであることが判明した。従って、一過性高グリシン血症はGLDC遺伝子のheteroinsuficiencyが基盤にあると考えられる。中枢神経系で生理的にグリシン濃度が高まる新生児期にグリシンの分解能力の低いこれらの新生児が発症するものと考えられた。NKHの両親は保因者であり、GLDCのヘテロ接合体であるが、必ずしも一過性高グリシン血症を発症するわけでない。このことは、一過性NKH発症の背景にはもう一つ未知の要因が関係しているものと考えられる。一方、重症型NKH患者ではもう一つのアレルに他の遺伝子変異を伴う事から、GLDC遺伝子の機能が失われ発症するものと推察された。他の遺伝子変異として、ミスセンス変異、ナンセンス変異、微小欠失など全部で26種類の遺伝子変異が現在までに同定されている。

Research Products

(11 results)

All Other

All Publications (11 results)

[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)
[Publications] Nagasaki Y.et al.: "Reversal of hypopitmentation in phynylketonuria mice by adenovirus-mediated gene transfer"Pediatric Research. 45,4. 465-473 (1999)
[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)
[Publications] Jackson AH.et al.: "A typical monketotic hyperglycinemia with normal CSF : plasam glycine ratio"Journal of Child Neurology. 14. 464-467 (1999)
[Publications] Kure S.et al.: "Tetrahydrobiopterine-responsive phenylalanine hydrosylase deficiency"Journal of Pediatrics. 135. 357-378 (1999)
[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)
[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)
[Publications] Von der Knaap et al.: "A biochemical marker for a leukoencephalopathy with vanishing white matter"Journal of Child Neurology. 14. 728-731 (1999)
[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)
[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)
[Publications] Takayanagi M.et al.: "Human glycine decarboxylase (GLDC) gene and its processed type pseudogene"Human Genetics. (in press).

1999 Fiscal Year Annual Research Report

グリシン脱炭酸酵素遺伝子の高頻度欠失領域と高グリシン血症の病型

Principal Investigator

呉 繁夫 東北大学, 大学院・医学系研究科, 助手 (10205221)

Research Products

[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)

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

[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)

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

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

[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)

[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)

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

[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)

[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)

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

呉繁夫東北大学, 大学院・医学系研究科, 助手 (10205221)