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Elucidation for genetic basis of infantile epileptic encephalopathy by using comprehensive genetic analysis

Research Project

Project/Area Number 25293085
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Human genetics
Research InstitutionHamamatsu University School of Medicine (2015)
Yokohama City University

Principal Investigator

Saitsu Hirotomo  浜松医科大学, 医学部, 教授 (40402838)

Co-Investigator(Renkei-kenkyūsha) KODERA HIROFUMI  横浜市立大学, 博士研究員 (70637884)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords遺伝子変異 / てんかん性脳症 / エクソーム解析 / 乳児てんかん / 遺伝学 / てんかん / ゲノム
Outline of Final Research Achievements

Target capture analysis against 35 or 50 epilepsy genes and whole exome sequencing was performed in 104 and 623 cases with infantile epileptic encephalopathy, respectively. We identified several new disease causing genes (GNAO1, SLC35A2, PIGA, COG2, KCNB1). With our analysis along with world-wide progress of genetics of infantile epileptic encephalopathy, approximately 45 % of cases could be genetically diagnosed.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (44 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (25 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 25 results,  Acknowledgement Compliant: 13 results,  Open Access: 8 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Sheba Medical Center/Wolfson Medical Center/Schneider's Children Medical Center(イスラエル)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] High prevalence of genetic alterations in early-onset epileptic encephalopathies associated with infantile movement disorders.2016

    • Author(s)
      Kobayashi Y, Tohyama J, Kato M, Akasaka N, Magara S, Kawashima H, Ohashi T, Shiraishi H, Nakashima M, Saitsu H, Matsumoto N.
    • Journal Title

      Brain Dev.

      Volume: 38 Issue: 7 Pages: 285-92

    • DOI

      10.1038/jhg.2016.27

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia2016

    • Author(s)
      Makrythanasis P, Kato M, Zaki MS, Saitsu H, Nakamura K, Santoni FA, Miyatake S, Nakashima M, Issa MY, Guipponi M, Letourneau A, Logan CV, Roberts N, Parry DA, Johnson CA, Matsumoto N, Hamamy H, Sheridan E, Kinoshita T, Antonarakis SE, Murakami Y.
    • Journal Title

      Am J Hum Genet

      Volume: 98 Issue: 4 Pages: 615-626

    • DOI

      10.1016/j.ajhg.2016.02.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phenotypic spectrum of GNAO1 variants: Epileptic encephalopathy to involuntary movements with severe developmental delay2016

    • Author(s)
      Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina M, Ogata K, Matsumoto N
    • Journal Title

      Eur J Hum Genet

      Volume: 24 Issue: 1 Pages: 129

    • DOI

      10.1038/ejhg.2015.92

    • URL

      https://pure.teikyo.jp/en/publications/06a45aed-f2e5-424a-b8d1-3e9a6923fdc5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ineffective quinidine therapy in early onset epileptic encephalopathy with KCNT1 mutation.2016

    • Author(s)
      Chong PF, Nakamura R, Saitsu H, Matsumoto N, Kira R.
    • Journal Title

      Ann Neurol.

      Volume: 79 Issue: 3 Pages: 502-3

    • DOI

      10.1002/ana.24598

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations2016

    • Author(s)
      Inui T, Kobayashi S, Ashikari Y, Sato R, Endo W, Uematsu M, Oba H, Saitsu H, Matsumoto N, Kure S, Haginoya K.
    • Journal Title

      Brain Dev.

      Volume: 38 Issue: 5 Pages: 520

    • DOI

      10.1016/j.braindev.2015.11.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] De novo DNM1 mutations in two cases of epileptic encephalopathy.2015

    • Author(s)
      Nakashima M, Kouga T, Lourenço CM, Shiina M, Goto T, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Ogata K, Osaka H, Matsumoto N.
    • Journal Title

      Epilepsia

      Volume: Epub 2015 Nov 27. Issue: 1

    • DOI

      10.1111/epi.13257

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing.2015

    • Author(s)
      Saitsu, H., T. Akita, J. Tohyama, H. Goldberg-Stern, Y. Kobayashi, R. Cohen, M. Kato, C. Ohba, S. Miyatake, Y. Tsurusaki, M. Nakashima, N. Miyake, A. Fukuda, and N. Matsumoto
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 15199-15199

    • DOI

      10.1038/srep15199

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] De novo KCNT1 mutations in early-onset epileptic encephalopathy.2015

    • Author(s)
      Ohba C, Kato M, Takahashi N, Osaka H, Shiihara T, Tohyama J, Nabatame S, Azuma J, Fujii Y, Hara M, Tsurusawa R, Inoue T, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N.
    • Journal Title

      Epilepsia

      Volume: 56(9) Issue: 9

    • DOI

      10.1111/epi.13072

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb2015

    • Author(s)
      Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M, Kitaura H, Shiina M, Shirozu H, Masuda H, Watanabe K, Ohba C, Tsurusaki Y, Miyake N, Zheng Y, Sato T, Takebayashi H, Ogata K, Kameyama S, Kakita A, Matsumoto N
    • Journal Title

      Ann. Neurol.

      Volume: 78 Issue: 3 Pages: 375-386

    • DOI

      10.1002/ana.24444

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders2015

    • Author(s)
      Ohba C, Shiina M, Tohyama J, Haginoya K, Lerman-Sagie T, Okamoto N, Blumkin L, Lev D, Mukaida S, Nozaki F, Uematsu M, Onuma A, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Kato M, Ogata K, Saitsu H, Matsumoto N
    • Journal Title

      Epilepsia

      Volume: 印刷中 Issue: 6 Pages: 841-848

    • DOI

      10.1111/epi.12987

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] SPTAN1 encephalopathy: distinct phenotypes and genotypes2015

    • Author(s)
      Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H
    • Journal Title

      Journal of Human Genetics

      Volume: 60(4) Issue: 4 Pages: 167-173

    • DOI

      10.1038/jhg.2015.5

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy.2015

    • Author(s)
      Kodera H, Osaka H, Iai M, Aida N, Yamashita A, Tsurusaki Y, Nakashima M, Miyake N, Saitsu H, Matsumoto N.
    • Journal Title

      Journal of Human Genetics

      Volume: 60 Pages: 97-101

    • NAID

      40020368024

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Compound heterozygous BRAT1 mutations cause familial Ohtahara syndrome with hypertonia and microcephaly.2014

    • Author(s)
      Saitsu H, Yamashita S, Tanaka Y, Tsurusaki Y, Nakashima M, Miyake N, Matsumoto N.
    • Journal Title

      Journal of Human Genetics

      Volume: 59 Issue: 12 Pages: 687-690

    • DOI

      10.1038/jhg.2014.91

    • NAID

      40020308684

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 32014

    • Author(s)
      Nakashima M, Kashii H, Murakami Y, Kato M, Tsurusaki Y, Miyake N, Kubota M, Kinoshita T, Saitsu H, Matsumoto N.
    • Journal Title

      Neurogenet

      Volume: 15(3) Issue: 3 Pages: 193-200

    • DOI

      10.1007/s10048-014-0408-y

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Causative novel PNKP mutations and concomitant PCDH15 mutations in a patient with microcephaly with early-onset seizures and developmental delay syndrome and hearing loss2014

    • Author(s)
      Nakashima M, Takano K, Osaka H, Aida N, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N.
    • Journal Title

      J Hum Genet

      Volume: 59(8) Issue: 8 Pages: 471-474

    • DOI

      10.1038/jhg.2014.51

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Early onset epileptic encephalopathy caused by de novo SCN8A mutations2014

    • Author(s)
      Ohba C, Kato M, Takahashi S, Lerman-Sagie T, Lev D, Terashima H, Kubota M, Kawawaki H, Matsufuji M, Kojima Y, Tateno A, Goldberg-Stern H, Straussberg R, Marom D, Leshinsky-Silver E, Nakashima M, Nishiyama K, Tsurusaki Y, Miyake N, Tanaka F, Matsumoto N, Saitsu H:
    • Journal Title

      Epilepsia

      Volume: 55 Issue: 7 Pages: 994-1000

    • DOI

      10.1111/epi.12668

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PIGA mutations cause early-onset epileptic encephalopathies and distinctive features2014

    • Author(s)
      Kato M, Saitsu H, Murakami Y , Kikuchi K, Watanabe S, Iai M, Miya K, Matsuura R, Takayama R, Ohba C, Nakashima M, Tsurusaki Y, Miyake N, Hamano S, Osaka H, Hayasaka K, Kinoshita T, Matsumoto N.
    • Journal Title

      Neurology

      Volume: 82(18) Issue: 18 Pages: 1587-1596

    • DOI

      10.1212/wnl.0000000000000389

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability and, autistic behaviors and epilepsy2014

    • Author(s)
      Nakajima J, Okamoto N, Tohyama J, Kato M, Arai H, Funahashi O, Tsurusakia Y, Nakashima M, Kawashima H, Saitsu H, Matsumoto N, Miyake N.
    • Journal Title

      Clin Genet

      Volume: 87(4) Issue: 4 Pages: 356-361

    • DOI

      10.1111/cge.12394

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.2014

    • Author(s)
      Nakamura, K.Osaka, H.Murakami, Y.Anzai, R.Nishiyama, K.Kodera, H.Nakashima, M.Tsurusaki, Y.Miyake, N.Kinoshita, T.Matsumoto, N. and Saitsu, H
    • Journal Title

      Epilepsia

      Volume: 55 Issue: 2 Pages: 13-17

    • DOI

      10.1111/epi.12508

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RBPJ is disrupted in a case of proximal 4p deletion syndrome with epilepsy2014

    • Author(s)
      Nakayama T, Saitsu H, Endo W, Kikuchi A, Uematsu M, Haginoya K, Hino-Fukuyo N, Kobayashi T, Iwasaki M, T ominaga T, Kure S, Matsumoto N
    • Journal Title

      Brain Dev

      Volume: 36(6) Issue: 6 Pages: 532-6

    • DOI

      10.1016/j.braindev.2013.07.009

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy2013

    • Author(s)
      Kodera H, Nakamura K, Osaka H, Maegaki Y, Haginoya K, Mizumoto S, Kato M, Okamoto N, Iai M, Kondo Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, Sugahara K, Yuasa I, Wada Y, Matsumoto N, Saitsu H.
    • Journal Title

      Hum Mutat

      Volume: 34 Issue: 12 Pages: 1708-1714

    • DOI

      10.1002/humu.22446

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.2013

    • Author(s)
      Nakamura K, et al., Miyake N, et al., *Matsumoto N, *Saitsu H (* denotes co-corresponding).
    • Journal Title

      Neurology

      Volume: 81 Issue: 11 Pages: 992-998

    • DOI

      10.1212/wnl.0b013e3182a43e57

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy.2013

    • Author(s)
      Nakamura, K., et al.,
    • Journal Title

      Am. J. Hum. Genet.

      Volume: 93 Issue: 3 Pages: 496-505

    • DOI

      10.1016/j.ajhg.2013.07.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Target capture sequencing for detection of mutations and copy number changes causing early-onset epileptic encephalopathy.2013

    • Author(s)
      Kodera H, Kato M, Nord AS, Walsh T, Lee M, Yamanaka G, Tohyama J, Nakamura K, Nakagawa E, Ikeda T, Ben-Zeev B, Lev D, Lerman-Sagie T, Straussberg R, Tanabe S, Ueda K, Amamoto M, Ohta S, Nododa Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, King M-C, Matsumoto N, *Saitsu H.
    • Journal Title

      Epilepsia

      Volume: 54 Issue: 7 Pages: 1262-1269

    • DOI

      10.1111/epi.12203

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation2013

    • Author(s)
      Kato M, …Saitsu H.
    • Journal Title

      Epilepsia

      Volume: in press Issue: 7 Pages: 1282-7

    • DOI

      10.1111/epi.12200

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Somatic mutations in the MTOR gene cause focal cortical dysplasia type IIb2015

    • Author(s)
      Hirotomo Saitsu et al.
    • Organizer
      American Epilepsy Society
    • Place of Presentation
      Philadelphia
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GNAO1変異が引き起こす表現型の広がり:てんかん性脳症から不随意運動を伴う発達遅滞まで2015

    • Author(s)
      才津浩智等
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 次世代シークエンスが切り開く 疾患の原因解明2015

    • Author(s)
      才津浩智
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay2015

    • Author(s)
      Hirotomo Saitsu et al.
    • Organizer
      American Society of Human Genetics
    • Place of Presentation
      Baltimore
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay2015

    • Author(s)
      Hirotomo Saitsu et al.
    • Organizer
      International Workshop on Advanced Genomics
    • Place of Presentation
      学術総合センター 一橋講堂(東京都)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 乳幼児てんかん性脳症の遺伝要因の解明2015

    • Author(s)
      才津 浩智
    • Organizer
      第67回大阪小児てんかん研究会
    • Place of Presentation
      ホテルグランヴィア大阪、大阪
    • Year and Date
      2015-03-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] エクソーム解析による包括的遺伝子診断2014

    • Author(s)
      才津 浩智
    • Organizer
      日本人類遺伝学会第59回大会・日本遺伝子診療学会第21回大会
    • Place of Presentation
      タワーホール船堀、東京
    • Year and Date
      2014-11-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 次世代シークエンサーを用いた包括的遺伝子診断2014

    • Author(s)
      才津 浩智
    • Organizer
      2014アジレントゲノミックスフォーラム
    • Place of Presentation
      国際ファッションセンター、東京
    • Year and Date
      2014-06-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] WDR45変異によるオートファジー障害が脳内に鉄沈着を伴う神経変性症を引き起こす2014

    • Author(s)
      才津 浩智
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2014-05-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 次世代シークエンサーによるてんかんを伴う知的障害の網羅的遺伝子解析2014

    • Author(s)
      才津 浩智
    • Organizer
      第117回日本小児科学会学術集会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2014-04-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 加速する発達期脳神経疾患の原因解明2013

    • Author(s)
      才津 浩智
    • Organizer
      第58回日本人類遺伝学会
    • Place of Presentation
      江陽グランドホテル、仙台
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 次世代シークエンサーを用いた遺伝子診断2013

    • Author(s)
      才津 浩智
    • Organizer
      NGS現場の会第3回研究会
    • Place of Presentation
      神戸国際会議場、神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 遺伝子検査と新規遺伝子同定におけるイルミナシークエンサーの運用2013

    • Author(s)
      才津 浩智
    • Organizer
      イルミナ 次世代シーケンサーユーザーフォーラム
    • Place of Presentation
      東京 ヒューリックホール、東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 早期発症てんかん性脳症の遺伝学的解明 ~次世代シークエンサーの活用~2013

    • Author(s)
      才津 浩智
    • Organizer
      第55回日本小児神経学会学術集会
    • Place of Presentation
      iichiko総合文化センター、大分
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 増刊号 臨床医が知っておきたい先天異常 「次世代シークエンスによる遺伝子診断の進歩」2013

    • Author(s)
      才津 浩智
    • Total Pages
      279
    • Publisher
      日本小児医事出版社
    • Related Report
      2013 Annual Research Report
  • [Book] 実験医学増刊 ゲノム 医学・生命科学研究 「次世代シークエンサーによるメンデル遺伝性疾患の責任遺伝子解明2013

    • Author(s)
      大場 ちひろ、才津 浩智、松本 直通
    • Total Pages
      2543
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Remarks] 医学群 遺伝学 才津准教授、松本教授ら研究グループが、小児の難治性てんかんの原因遺伝子を発見

    • URL

      http://www.yokohama-cu.ac.jp/univ/pr/press/130827.html

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 小児期のてんかんおよび不随意運動をきたす疾患の検出方法2013

    • Inventor(s)
      松本直通、才津浩智
    • Industrial Property Rights Holder
      公立大学法人横浜市立大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-123660
    • Filing Date
      2013-06-12
    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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