Pathological role of interneurons in pediatric brain disorders

2008 Fiscal Year Final Research Report

• Project/Area Number: 19591198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: KATOH Mitsuhiro Yamagata University, 医学部, 講師 (10292434)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Toshio 理化学研究所, 応用システムバイオロジー研究チーム, チームリーダー (00311340) ; NAKAMURA Kazuyuki 山形大学, 医学部, 医員 (20436215)
• Project Period (FY): 2007 – 2008
• Keywords: 小児神経学 / 年齢依存性てんかん性脳症 / 大田原症候群 / ウエスト症候群 / 介在ニューロン / ARX 遺伝子 / ポリアラニン病

Research Abstract

新生児期に難治性のてんかん発作を発症し重度の発達遅滞をきたす大田原症候群の原因遺伝子(ARX)を明らかにした。ARX は大脳介在ニューロン(iN)の発生に関与する。太田原症候群の病態にiN が関与することが証明された。大田原症候群は精神遅滞(2~3残基追加)やウエスト症候群(7残基追加)よりも長いポリアラニン配列の伸長変異(11残基追加)を有し,年齢依存性の発症機序・病態が反復配列の伸長数の違いによることを明らかにした。

Research Products

• [Journal Article] Two new cases of pure 1q terminal deletion presenting with brain malformations (2008)
  • Author(s): Hiraki Y, Okamoto N, Ida T, Nakata Y, Kamada M, Kanemura Y, Yamasaki M, Fujita H, Nishimura G, Kato M, Harada N, Matsumoto N
  • Journal Title: Am J Med Genet A 146 Pages: 1241-1247
  • Peer Reviewed
• [Journal Article] De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy (2008)
  • Author(s): Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, Uruno K, Kumada S, Nishiyama K, Nishimura A, Okada I, Yoshimura Y, Hirai S, Kumada T, Hayasaka K, Fukuda A, Ogata K, Matsumoto N
  • Journal Title: Nat Genet 40 Pages: 782-788
  • Peer Reviewed
• [Journal Article] Early onset West syndrome with cerebral hypomyelination and reduced cerebral white matter (2008)
  • Author(s): Tohyama J, Akasaka N, Osaka H, Maegaki Y, Kato M, Saito N, Yamashita S, Ohno K
  • Journal Title: Brain Dev 30 Pages: 349-355
  • Peer Reviewed
• [Journal Article] Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus (2007)
  • Author(s): Guerrini R, Moro F, Kato M, Barkovich AJ, Shiihara T, McShane MA, Hurst J, Loi M, Tohyama J, Norci V, Hayasaka K, Kang UJ, Das S, Dobyns WB
  • Journal Title: Neurology 69 Pages: 427-33
  • Peer Reviewed
• [Journal Article] A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome) (2007)
  • Author(s): Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K.
  • Journal Title: Am J Hum Genet 81 Pages: 361-6
  • Peer Reviewed
• [Journal Article] Clinical and molecular cytogenetic characterization of two patients with non-mutational aberrations of the FMR2 gene (2007)
  • Author(s): Honda S, Hayashi S, Kato M, Niida Y, Hayasaka K, Okuyama T, Imoto I, Mizutani S, Inazawa J.
  • Journal Title: Am J Med Genet Part A 143A Pages: 687-693
  • Peer Reviewed
• [Journal Article] A case of acute cerebellitis accompanied by autoantibodies against glutamate receptor delta 2 (2007)
  • Author(s): Shimokaze T, Kato M, Yoshimura Y, Takahashi Y, Hayasaka K
  • Journal Title: Brain Dev 29 Pages: 224-226
  • Peer Reviewed
• [Journal Article] Acute cerebellar ataxia and consecutive cerebellitis produced by glutamate receptor delta2 autoantibody (2007)
  • Author(s): Shiihara T, Kato M, Konno A, Takahashi Y, Hayasaka K.
  • Journal Title: Brain Dev 29 Pages: 254-256
  • Peer Reviewed
• [Journal Article] 神経細胞移動障害の分子機構 (2007)
  • Author(s): 加藤光広
  • Journal Title: 日本小児科学会雑誌 111(11) Pages: 1361-1374
• [Presentation] Interneuronopathy bridging the gap between brain malformations and functional disorders (2008)
  • Author(s): Kato M
  • Organizer: The 3rd German-Japanese Symposium Pediatric Neurology
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080909-10
• [Presentation] Candidate genes (ARX, CDKL5, and SLC25A22) mutation screening for early-onset epileptic encephalopathy (2008)
  • Author(s): Kato M, Nakamura K, Matsumoto N, Osaka H, Hayasaka K
  • Organizer: The 4th Congress of the Asian Society for Pediatric Research
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 20080503-06
• [Presentation] Severe mutations of ARX are associated with an abnormal phenotype in most heterozygous females but not in mothers of affected children (2007)
  • Author(s): Sudi J, Kato M, Mancini G, Toutain A, Das S, Christian S, Dobyns W
  • Organizer: 57th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071023-27
• [Presentation] Early infantile epileptic encephalopathy with suppression-burst(Ohtahara syndrome)is caused by a longer polyalanine expansion mutation in the ARX gene (2007)
  • Author(s): Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Kumada S, Kubota M, Nakamura K, Hayasaka K
  • Organizer: 57th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071023-27
• [Presentation] Construction of research resource depository in Japan and molecular genetics study on genetic diseases with mental retardation (2007)
  • Author(s): Goto Y-I, Nakagawa E, Takano K, Inazawa J, Okazawa H, Kato M, Kubota T, Kurosawa K, Saitoh S, Nanba E, Matsumoto N, Toda T, Wada T
  • Organizer: The 13th International Workshop on Fragile X and X-Linked Mental Retardation
  • Place of Presentation: Venezia Lido, Italy
  • Year and Date: 20071003-06
• [Presentation] A longer polyalanine expansion mutation in the ARX gene causes Ohtahara syndrome (2007)
  • Author(s): Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K
  • Organizer: The 10th Annual Meeting of the Infantile Seizure Society International Symposium on Biology of Seizure Susceptibility
  • Place of Presentation: Tokyo
  • Year and Date: 20070407-08
• [Presentation] Early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome) is caused by longer polyalanine expansion mutation of the ARX gene than West syndrome (2007)
  • Author(s): Kato M, Saitoh S, Shiraishi H, Tohyama J, Akasaka N, Hayasaka K
  • Organizer: The 9th Asian and Oceanian Congress of Child Neurology
  • Place of Presentation: Cebu
  • Year and Date: 20070124-27
• [Book] Genetic etiology of age-dependent epileptic encephalopathies in infancy : longer polyalanine expansion in ARX causes earlier onset and more severe phenotype. Biology of Seizure Susceptibility in Developing Brain. Progress in Epileptic Disorders Series (2008)
  • Author(s): Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K
  • Total Pages: 75-86
  • Publisher: Editions John Libbey Eurotext, Montrouge (Paris), France
• [Book] 脳形成障害.五十嵐隆総編集岡明専門編集「小児科臨床ピクシス(3)小児てんかんの最新医療」2章てんかんの原因 (2008)
  • Author(s): 加藤光広
  • Total Pages: 28-31
  • Publisher: 中山書店 東京
• [Book] 神経系の発生,中枢神経系奇形, migrationの異常.有馬正高監修「小児神経学」2章 (2008)
  • Author(s): 加藤光広
  • Total Pages: 30-39
  • Publisher: 神経形成異常診断と治療社
• [Book] 脳回形成異常(無脳回, 厚脳回, 多小脳回, 滑脳症).『小児中枢神経疾患の画像診断2008』 (2007)
  • Author(s): 加藤光広
  • Total Pages: 198-202
  • Publisher: 小児内科 東京医学社
• [Book] 中枢神経系の発生異常の遺伝学的背景. 『小児神経学の進歩』第36集 (2007)
  • Author(s): 加藤光広
  • Total Pages: 47-57
  • Publisher: 診断と治療社
• [Remarks]
  • URL: http://www.id.yamagata-u.ac.jp/Ped/pedi.top.htm