Identification of responsive genes for infantile epilepsy using genomic microarray

• Project/Area Number: 20790267
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human genetics
• Research Institution: Yokohama City University
• Principal Investigator: SAITSU Hirotomo Yokohama City University, 医学部, 助教 (40402838)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ゲノム / てんかん / 乳児 / 大田原症候群 / STXBP1 / 太田原症候群 / 新生児

Research Abstract

Thorough genomic microarray analysis of patients with infantile epilepsy, we identified a de novo microdeletion at 9q33.3-q34.11 in a patient with Ohtahara syndrome. Among the genes mapped within the deletion, STXBP1 was found to be mutated in four patients with Ohtahara syndrome, indicating that mutations of STXBP1 caused Ohtahara syndrome (Saitsu et al., Nature Genetics, 2008). This finding raised a novel mechanism in which aberration of synaptic vesicle release would cause epilepsy.

Research Products

• [Journal Article] De novo deletion of 1q24. 3-q31. 2 in a patient with severe growth retardation. (2010)
  • Author(s): Nishimura A, Hiraki Y, Shimoda H, Nishimura G, Tadaki H, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N
  • Journal Title: Am J Med Genet A. 152A(5) Pages: 1322-5
• [Journal Article] Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly. (2010)
  • Author(s): Komoike Y, Fujii K, Nishimura A, Hiraki Y, Hayashidani M, Shimojima K, Nishizawa T, Higashi K, Yasukawa K, Saitsu H, Miyake N, Mizuguchi T, Matsumoto N, Osawa M, Kohno Y, Higashinakagawa T, Yamamoto T
  • Journal Title: Genesis 48(4) Pages: 233-43
• [Journal Article] Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain. (2010)
  • Author(s): Zhao L, Saitsu H, Sun X, Shiota K, Ishibashi M
  • Journal Title: Mech Dev 127(1-2) Pages: 62-72
  • NAID: 120001887646
• [Journal Article] De novo deletion of 1q24.3-q31.2 in a patient with severe growth retardation. (2010)
  • Author(s): 西村章
  • Journal Title: Am J Med Genet A. 152A(5) Pages: 1322-1325
  • Peer Reviewed
• [Journal Article] Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly. (2010)
  • Author(s): 蒋池勇太
  • Journal Title: Genesis 48(4) Pages: 233-243
  • Peer Reviewed
• [Journal Article] Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain. (2010)
  • Author(s): 趙蘭英
  • Journal Title: Mech Dev 127(1-2) Pages: 62-72
  • Peer Reviewed
• [Journal Article] Characterization of the complex 7q21. 3 rearrangement in a patient with bilateral split foot malformation and hearing loss. (2009)
  • Author(s): Saitsu H, Kurosawa K, Kawara H, Eguchi M, Mizuguchi T, Harada N, Kaname T, Kano H, Miyake N, Toda T, Matsumoto N
  • Journal Title: Am J Med Genet A 149A(6) Pages: 1224-1230
• [Journal Article] Genetic screening of 104 patients with congenitally malformed hearts revealed a fresh mutation of GATA4 in toses with atrial septal defects. (2009)
  • Author(s): 浜之上はるか
  • Journal Title: Cardiol Young 13 Pages: 1-4
  • Peer Reviewed
• [Journal Article] Characterization of the complex 7q21.3 rearrangement in a patient with bilateral split foot malformation and hearing loss (2009)
  • Author(s): 才津浩智
  • Journal Title: Am J Med Genet A. 149A(6) Pages: 1224-1230
  • Peer Reviewed
• [Journal Article] A locus for ophthalmoacromelic syndrome mapped to 10p11.23 (2009)
  • Author(s): 浜之上はるか
  • Journal Title: Am J Med Genet A 149A(3) Pages: 336-342
  • Peer Reviewed
• [Journal Article] Hedgehog signaling is involved in development of the neocortex. (2008)
  • Author(s): Komada M, Saitsu H, Kinboshi M, Miura T, Shiota K, Ishibashi M
  • Journal Title: Development 135(16) Pages: 2717-27
• [Journal Article] CDKL5 disruption by t(X;18) in a girl with West syndrome. (2008)
  • Author(s): Nishimura A, Takano T, Mizuguchi T, Saitsu H, Takeuchi Y, Matsumoto N
  • Journal Title: Clin Genet 74(3) Pages: 288-90
• [Journal Article] Alu-related 5q35 microdeletions in Sotos syndrome. (2008)
  • Author(s): Mochizuki J, Saitsu H, Mizuguchi T, Nishimura A, Visser R, Kurotaki N, Miyake N, Unno N, Matsumoto N
  • Journal Title: Clin Genet 74(4) Pages: 384-91
• [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: Nature Genetics 40(6) Pages: 782-8
• [Journal Article] Involvement of the axially condensed tail bud mesenchyme in normal and abnormal human posterior neural tube development. (2008)
  • Author(s): Saitsu H, Shiota K
  • Journal Title: Congenit Anom (Kyoto) 48(1) Pages: 1-6
  • NAID: 10027386860
• [Journal Article] Expression dynamics of the LIM-homeobox genes, Lhx1 and Lhx9, in the diencephalon during chick development. (2008)
  • Author(s): Sun X, Saitsu H, Shiota K, Ishibashi M
  • Journal Title: Int J Dev Biol 52(1) Pages: 33-41
• [Journal Article] Microarray comparative genomic hybridization analysis of 59 patients with schizophrenia (2008)
  • Author(s): 水口剛
  • Journal Title: J Hum Genet 53(10)
  • Peer Reviewed
• [Journal Article] Hedgehog signaling is involved in development of the neocortex (2008)
  • Author(s): 駒田致和
  • Journal Title: Development 135(16) Pages: 2717-27
  • Peer Reviewed
• [Journal Article] CDKL5 disruption by t(X ; 18) in a girl with West syndrome (2008)
  • Author(s): 西村章
  • Journal Title: Development 74(3) Pages: 288-290
  • Peer Reviewed
• [Journal Article] Alu-related 5q35 microdeletions in Sotos syndrome (2008)
  • Author(s): 望月純子
  • Journal Title: Clin Genet 74(4) Pages: 384-391
  • Peer Reviewed
• [Journal Article] De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy (2008)
  • Author(s): 才津浩智
  • Journal Title: Nature Genetics 40(6) Pages: 782-788
  • Peer Reviewed
• [Presentation] Characterization of the complex 7q21. 3 rearrangement in a patient with bilateral split-foot malformation and hearing loss. (2009)
  • Author(s): Saitsu H, Kurosawa K, Kawara H, Eguchi M, Mizuguchi T, Harada N, Kaname T, Kano H, Miyake N, Toda T, Matsumoto N
  • Organizer: 59th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2009-10-21
• [Presentation] Characterization of the complex 7q21.3 rearrangement in a patient with bilateral split-foot malformation and hearing loss. (2009)
  • Author(s): Saitsu H
  • Organizer: 59^<th> Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: ハワイ アメリカ
  • Year and Date: 2009-10-21
• [Presentation] 裂足と聴覚障害を呈する患者に認められた7q21.3領域の染色体構造異常. (2009)
  • Author(s): 才津浩智
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 品川
  • Year and Date: 2009-09-26
• [Presentation] Analysis of congenital anomalies by using microarray (2009)
  • Author(s): 才津浩智
  • Organizer: The 20^<th> Fukuoka International Synposium on Pediatric/Maternal-Child Health Research
  • Place of Presentation: 福岡
  • Year and Date: 2009-08-29
• [Presentation] 発生生物学からみたDysmorphology～形態形成と遺伝子発現調節～ (2009)
  • Author(s): 才津浩智
  • Organizer: 第49回日本先天異常学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2009-06-26
• [Presentation] Analysis of congenital anomalies by using microarray (2009)
  • Author(s): Saitsu H
  • Organizer: The 20th Fukuoka International Synposium on Pediatric/Maternal-Child Health Research
  • Place of Presentation: Fukuoka, Symposium
• [Presentation] 発生生物学からみたDysmorphology～形態形成と遺伝子発現調節～ (2009)
  • Author(s): 才津浩智
  • Organizer: 第49回日本先天異常学会学術集会
  • Place of Presentation: 鹿児島, シンポジウム
• [Presentation] De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy (2008)
  • Author(s): 才津浩智
  • Organizer: 58^<th> Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: フィラデルフィア アメリカ
  • Year and Date: 2008-11-12
• [Presentation] 転座を有する裂足患者のゲノム解析 (2008)
  • Author(s): 才津浩智
  • Organizer: 第48回日本先天異常学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-29
• [Presentation] 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
  • Organizer: 58th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Philadelphia, USA
• [Presentation] STXBP1(MUNC18-1)をコードする遺伝子のde novo変異によって大田原症候群が引き起こされる (2008)
  • Author(s): 才津浩智, 加藤光広, 水口剛, 濱田恵輔, 小坂仁, 遠山潤, 宇留野勝久, 熊田聡子, 西山精視, 西村章, 岡田一平, 吉村有紀子, 平井秀一, 熊田竜郎, 早坂清, 福田敦夫, 緒方一博, 松本直通
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Patent(Industrial Property Rights)] 大脳白質異常を伴う点頭てんかんの検出方法 (2009)
  • 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 Number: 2009-146055
  • Filing Date: 2009-06-19
• [Patent(Industrial Property Rights)] 新生児期～乳児期発症の難治性てんかんの検出方法 (2007)
  • 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 Number: 2007-340147
  • Filing Date: 2007-12-28
• [Patent(Industrial Property Rights)] 新生児期〜乳児期発症の難治性てんかんの検出方法 (2007)
  • 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 Number: 2007-340147
  • Filing Date: 2007-12-28