Molecular and biochemical analysis of mutants identified in Cardio-facio-cutaneous syndrome

• Project/Area Number: 19689022
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: NIIHORI Tetsuya Tohoku University, 大学院医学系研究科, 助教 (40436134)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2007: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 遺伝 / 先天異常学 / 先天奇形症候群 / CFC症候群 / ヌーナン症候群 / コステロ症候群 / シグナル伝達 / 遺伝子変異

Research Abstract

CFC症候群および臨床的に類似したヌーナン症候群、コステロ症候群患者(疑い含む)の検体を収集し、原因遺伝子解析を行った。ヌーナン症候群の原因遺伝子として同定されたSOS1遺伝子については、ヌーナン症候群患者24人中4人のみならずヌーナン/CFC症候群患者2人およびCFC症候群1人にも変異を同定した。また、CFC患者の遺伝子変異がどのように機能しているか解析した。さらに新しい原因遺伝子を求め、候補遺伝子を解析した。

Research Products

• [Journal Article] The RAS/MAPK syndromes : novel roles of the RAS pathway in human genetic disorders. (2008)
  • Author(s): Aoki Y, Niihori T, Narumi Y, Kure S, Matsubara Y
  • Journal Title: Hum Mutat 29 Pages: 992-1006
  • Peer Reviewed
• [Journal Article] Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome. (2008)
  • Author(s): Narumi Y, Aoki Y, Niihori T, Sakurai M, Cave H, Verloes A, Nishio K, Ohashi H, Kurosawa K, Okamoto N, Kawame H, Mizuno S, Kondoh T, Addor MC, Coeslier-Dieux A, Vincent-Delorme C, Tabayashi K, Aoki M, Kobayashi T, Guliyeva A, Kure S, Matsubara Y
  • Journal Title: J Hum Genet 53 Pages: 834-41
  • NAID: 10021929483
  • Peer Reviewed
• [Journal Article] The RAS/MAPK syndromes : novel roles of the RAS pathway in humangenetic disorders (2008)
  • Author(s): Aoki Y, et.al.
  • Journal Title: Human Mutation 29 Pages: 992-1006
  • Peer Reviewed
• [Journal Article] Clinical manifestations in patients with SOS 1 mutations range from Noonan syndrome to CFC syndrome (2008)
  • Author(s): Narumi Y, et.al.
  • Journal Title: Journal of Human Genetics 53 Pages: 834-841
  • Peer Reviewed
• [Journal Article] Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome : Overlapping clinical manifestations with Costello syndrome. (2007)
  • Author(s): Narumi Y, Aoki Y, Niihori T, Neri G, Cave H, Verloes A, Nava C, Kavamura MI, Okamoto N, Kurosawa K, Hennekam RC, Wilson LC, Gillessen-Kaesbach G, Wieczorek D, Lapunzina P, Ohashi H, Makita Y, Kondo I, Tsuchiya S, Ito E, Sameshima K, Kato K, Kure S, Matsubara Y
  • Journal Title: Am J Med Genet A 143A Pages: 799-807
  • Peer Reviewed
• [Journal Article] Leukemia in cardio-facio-cutaneous (CFC) syndrome : a patient with a germline mutation in BRAF proto-oncogene. (2007)
  • Author(s): Makita Y, Narumi Y, Yoshida Y, Niihori T, Kure S, Fujieda K, Matsubara Y, Aoki Y
  • Journal Title: J Pediatr Hematol Oncol 29 Pages: 287-290
  • Peer Reviewed
• [Journal Article] CFC and Noonan syndromes due to mutations in RAS/MAPK signaling pathway : genotype/phenotype relationships and overlap with Costello syndrome. (2007)
  • Author(s): Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, Aoki Y, Matsubara Y, Arveiler B, Lacombe D, Pasmant E, Parfait B, Baumann C, Heron D, Sigaudy S, Toutain A, Rio M, Goldenberg A, Leheup B, Verloes A, Cave H
  • Journal Title: J Med Genet 44 Pages: 763-71
  • Peer Reviewed
• [Journal Article] Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK singalling pathway: genotype-phenotype relationships and overlap with Costello syndrome (2007)
  • Author(s): Nava C, et. al.
  • Journal Title: Journal of Medical Genetics 44 Pages: 763-771
  • Peer Reviewed
• [Journal Article] Leukemia in Cardio-facio-cutaneous (CFC) Syndrome: A Patient With a Germline Mutation in BRAF Proto-oncogene (2007)
  • Author(s): Makita Y, et. al.
  • Journal Title: Journal of Pediatric Hematology/Oncology 29 Pages: 287-290
  • Peer Reviewed
• [Journal Article] Molecular and Clinical Characterization of Cardio-Facio-Cutaneous (CFC) Syndrome: Overlapping Clinical Manifestations With Costello syndrome (2007)
  • Author(s): Narumi Y, et. al.
  • Journal Title: American Journal of Medical Genetics Part A 143A Pages: 799-807
  • Peer Reviewed
• [Presentation] Noonan症候群類縁疾患の包括的遺伝子解析とSOS1遺伝子変異 (2008)
  • Author(s): Afag Guliyeva, 青木洋子, 新堀哲也, 鳴海洋子, 小林朋子, 西尾公男, 大橋博文, 黒澤健司, 岡本伸彦, 川目裕, 水野誠司, 近藤達郎, 櫻井雅浩, 青木正志, 呉繁夫, 松原洋一
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-09-30
• [Presentation] Noonan症候群類縁疾患(The RAS/MAPK syndromes)の包括的遺伝子解析 (2008)
  • Author(s): 青木洋子
  • Organizer: 第15回日本遺伝子診療学会大会
  • Place of Presentation: 仙台市戦災復興記念館
  • Year and Date: 2008-08-01
• [Presentation] Noonan症候群類縁疾患(The'RAS/MAPK syndromes)の包括的遣伝子解析 (2008)
  • Author(s): 青木洋子, ら
  • Organizer: 第15回日本遺伝子診療学会大会
  • Place of Presentation: 仙台市戦災復興記念館
  • Year and Date: 2008-08-01
• [Presentation] Noonan症候群類縁疾患におけるSOS1遺伝子解析と臨床像の検討 (2008)
  • Author(s): 鳴海洋子、青木洋子、新堀哲也、小林朋子、西尾公男、櫻井雅浩、田林晄一、青木正志、大橋博文、岡本伸彦、川目裕、黒澤健司、呉繁夫、松原洋一
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-04-25
• [Presentation] Clinical spectrum of patients with SOS1 mutations ranges from Noonan syndrome to cardio-facio-cutaneous syndrome. (2008)
  • Author(s): Y. Narumi, Y. Aoki, T. Niihori, M. Sakurai, H. Cave, A. Verloes, K. Nishio, H. Ohashi, K. Kurosawa, N. Okamoto, H. Kawame, M.C. Addor, C. Vincent-Delorme, A. Coeslier-Dieux, M. Aoki, A. Guliyeva, T. Kobayashi, S. Kure, Y. Matsubara
  • Organizer: ASHG 58th Annual Meeting
  • Place of Presentation: フィラデルフィア、米国
• [Presentation] 自閉症を合併したcardio-facio-cutaneous(CFC)症候群の一例-BRAF変異と臨床症状の関連について (2008)
  • Author(s): 谷合弘子、水野誠司、浅井朋子、金山学、鷲見聡、新堀哲也、青木洋子、松原洋一
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Clinical spectrum of patients with SOS1 mutations ranges from Noonan syndrome to cardio-facio-cutaneous syndrome (2008)
  • Author(s): Narumi Y, et.al.
  • Organizer: ASHG 58^th Annual Meeting
  • Place of Presentation: フィラデルフィア、米国
• [Presentation] Noonan症候群類縁疾患の包括的遺伝子解析と診断システムの考案 (2007)
  • Author(s): 青木洋子, 新堀哲也, 鳴海洋子, 小林朋子, Afag Guliyeva, 川目裕, 黒澤健司, 大橋博文, 岡本伸彦, 西尾公男, 櫻井雅浩, 青木正志, 呉繁夫, 松原洋一
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2007-09-13
• [Presentation] Further molecular and clinical characterization in patients with Costello syndrome. (2007)
  • Author(s): Niihori T, et al.
  • Organizer: 1st International Costello Syndrome Research Symposium 2007
  • Place of Presentation: オレゴン健康科学大学(オレゴン州ポートランド)
  • Year and Date: 2007-07-21
• [Presentation] Further molecular and clinical characterization in patients with Costello syndrome (2007)
  • Author(s): Niihori T, et. al.
  • Organizer: 1st International Costello Syndrome Research Symposium 2007
  • Place of Presentation: オレゴン健康科学大学(オレゴン州ポートランド)
  • Year and Date: 2007-07-21