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Identification of the responsible genes for child epilepsy targeting abnormalities in the pore region of ion channels expressed in the central nerve system

Research Project

Project/Area Number 12470174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFukuoka University

Principal Investigator

HIROSE Shinichi  Fukuoka University, School of Medicine, Assistant professor, 医学部, 助教授 (60248515)

Co-Investigator(Kenkyū-buntansha) KANEKO Sunao  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (40106852)
YAMAKAWA Kazuhiro  Brain Science Institute RIKEN, Laboratory head, 脳科学総合研究センター, 神経遺伝チームリーダ (30241235)
MITSUDOME Akihisa  Fukuoka University, School of Medicine, Professor, 医学部, 教授 (30038749)
WADA Kazumaru  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (60241486)
杉山 博之  九州大学, 理学研究院, 教授 (20124224)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥6,200,000 (Direct Cost: ¥6,200,000)
KeywordsEpilepsy / Channel disease / GEFS^+ / Pyrogenestic spasm / ADNFLE / BFNC / CEFS+
Research Abstract

We have made the following discoveries based on the genetic analyses searching mutations of genes encoding ion channels expressed in the central nerve system. The specimens used were in the bank holding DNA samples obtained from patients with various epilepsy syndrome. Two novel mutations have been identified in the gene encoding a1 subunit of Na+ channel, SCN1A in patients with generalized epilepsy with febrile seizures plus (GEFS+). Furthermore, we found that the gene encoding a2 subunit of Na+ channel, SCN2A is associated with autosomal dominant epilepsy with febrile seizures plus. The mutation result in slow inactivation in the channel function thereby cause hyper inimitability of the channel. A number of mutations of SCN1A were also identified in Japanese patients with severe myoclonic epilepsy in infancy. We have done parallel studies where channel function harboring the mutations identified in the above series of study in in vitro system and transgenic animals were also generated.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hirose S., et al.: "The genetics of febrile seizures and related epilepsy syndromes"Brain Dev. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al.: "X-Linked mental retardation and epilepsy : Pathogenetic significance of ARX mutations"Brain Dev. 25. 161-165 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okada M., et al.: "Age-dependent modulation of hippocampal excitability by KCNQ-channels"Epilepsy Research. 58. 81-94 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al.: "Genetics abnormalities underlying familial epilepsy syndromes"Brain Dev. 24. 211-222 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaneko S., et al.: "Genetics of epilepsy : current status and perspectives"Neurosci Res. 44. 11-30 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsushima N., et al.: "Mutation (Ser284Leu) of neuronal nicotinic acetyicholine receptor α4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocyte"Epilepsy Res. 48. 181-186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al: "The genetics of febrile seizures and related Epilepsy syndromes"Brain Dev.. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al: "X-Linked mental retardation and epilepsy: Pathogenetic significance of ARX mutions"Brain Dev.. 25. 161-165 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okada M., et al: "Age-dependent modulation of hippocampal Excitability by KCNQ-channels"Epilepsy Research. 58. 81-94 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al: "Genetics abnormality underlying familial Epilepsy syndromeses"Brain Dev.. 24. 211-222 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaneko S., et al: "Genetics of epilepsy: current status and Perspectives"Neurosci Res. 44. 11-30 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsushima N., et al: "Mutation(Ser284Leu) of neuronal nicotinic acetylcholine receptor α4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocyte"Epilepsy Research. 48. 181-186 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose S., et al.: "The genetics of febrile seizures and related epilepsy syndromes"Brain Dev. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirose S., et al.: "X-Linked mental retardation and epilepsy : Pathogenetic significance of ARX mutations"Brain Dev. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada M., et al.: "Age-dependennt modulation of hippocampal excitability by KCNQ-channels"Epilepsy Research. 58. 81-94 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirose S., et al.: "Genetics abnormalities underlying familial epilepsy syndromes"Brain Dev. 24. 211-222 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaneko S., et al.: "Genetics of epilepsy : current status and perspectives"Neurosci Res. 44. 11-30 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsushima N., et al.: "Mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocyte"Epilepsy Res. 48. 181-186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugawara, T., Y.Tsurubuchi, K.L.Agarwala, M.Ito, G.Fukuma, E.Mazaki-Miyazaki, H.Nagafuji, M.Noda, K.Imoto, K.Wada, A.Mitsudome, S.Kaneko, M.Montal, K.Nagata, S.Hirose, K.Yamakawa: "A missense mutation of the Na^+ channel αII subunit gene Na_v1.2 in a patient with febrile and afebrile seizures causes channel dysfunction"Proc Natl Acad Sci USA. 98(11). 6384-6389 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara, T., E.Mazaki-Miyazaki, M.Ito, H.Nagafuji, G.Fukuma, A.Mitsudome, K.wada, S.Kaneko, S.Hirose, K.Yamakawa: "Na_v1.1 mutations cause febrile seizures associated with afebrile partial seizures"Neurology. 57. 703-705 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, M., H.Nagafuji, H.Okazawa, K.Yamakawa, T.Sugawara, E.Mazaki-Miyazaki, S.Hirose, G.Fukuma, A.Mitsudome, K.Wada, S.Kaneko: "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na^+)-channel α1 subunit gene, SCN1A"Epilepsy Res. 48. 15-23 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ganesh S, Shoda K, Amano K, Uchiyama A, Kumada S, Moriyama N, et al.: "Mutation screening for Japanese Lafora's disease patients : identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene"Mol Cell Probes. 15(5). 281-289 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsushima, N., S.Hirose, H.Iwata, G.Fukuma, M.Yonetani, C.Nagayama, W.Hamanaka, Y.Matsunaka, S.Kaneko, A.Mitsudome, H.Sugiyama: "Mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocytes"Epilepsy Res. 48. 181-186 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose S, Okada M, Kaneko S, Mitsudome A.: "Molecular Genetics of Human Familial Epilepsy Syndrome"Epilepsia. 43(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 廣瀬伸一: "Benign Familial Neonatal Convulsions(BFNC) BFNC1 & BFNC2"医学のあゆみ. 193. 515-521 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akiyoshi H,Iwata H,Fukuma G,Yonetani M,Wada K,Kaneko S,Mitsudome A,Hirose S.: "A novel SSCP variant (c.828G>A) within the M2 domain of the human neuronal nicotinic acetylcholine receptor a 4 subunit gene, CHRNA4."Hum Mutat. 16. 450 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirose S,Hamamoto K,Yoshida I,Inokuchi T,Kogo T,Mitsudome A.: "Late-onset type II glutaric aciduria with massive pericardial effusion associated with severe fatty liver."Acta Paediatr. 89. 887-888 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito M,Kobayashi K,Fujii T,Okuno T,Hirose S,Iwata H,Mitsudome A,Kaneko S.: "Electroclinical picture of autosomal dominant nocturnal frontal lobe epilepsy in a Japanese family."Epilepsia. 41. 52-58 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirose S,Zenri F,Akiyoshi H,Fukuma G,Iwata H,Inoue T,Yonetani M.Tsutsumi M,Muranaka H,Kurokawa T.Hanai T,Wada K,Kaneko S,Mitsudome A.: "A novel mutation of KCNQ3 (c.925T->C) in a Japanese family with benign familial neonatal convulsions."Ann Neurol. 47. 822-826 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirose S,Okada M,Kaneko S,Mitsudome A.: "Are some idiopathic epilepsies disorders of ion channels?: A working hypothesis."Epilepsy Res. 41. 191-204 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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