Epigenetic efects of the mutations in patients with the RAS/MAPK syndromes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23791148
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: NIIHORI Tetsuya 東北大学, 医学(系)研究科(研究院), 助教 (40436134)
• Project Period (FY): 2011 – 2013
• Keywords: 遺伝・先天異常学 / RAS/MAPK症候群

Research Abstract

We identified a total of nine missense mutations in RIT1 gene, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome and related conditions without mutations in known genes. Clinical manifestations in the mutation-positive individuals are consistent with those of Noonan syndrome, which are characterized by distinctive facial appearance, short stature and congenital heart defects. Seventy percent of mutation-positive individuals had hypertrophic cardiomyopathy, a high frequency compared with the 20% incidence in individuals with Noonan syndrome overall.

Research Products

• [Journal Article] TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia (2014)
  • Author(s): Ogata T, Niihori T, Tanaka N, Kawai M, Nagashima T, Funayama R, Nakayama K, Nakashima S, Kato F, Fukami M, Aoki Y, Matsubara Y
  • Journal Title: PLoS One Volume: 9(3) Pages: e91598
  • DOI: 10.1371/journal.pone.0091598
  • Peer Reviewed
• [Journal Article] A girl with Cardio-facio-cutaneous syndrome complicated with status epilepticus and acute encephalopathy (2014)
  • Author(s): Wakusawa K, Kobayashi S, Abe Y, Tanaka S, Endo W, Inui T, Iwaki M, Watanabe S, Togashi N, Nara T, Niihori T, Aoki Y, Haginoya K
  • Journal Title: Brain Dev Volume: 36(1) Pages: 61-3
  • DOI: 10.1016/j.braindev.2012.12.007
  • Peer Reviewed
• [Journal Article] Sequential analysis of amino acid substitutions with hepatitis B virus in association with nucleoside/nucleotide analog treatment detected by deep sequencing (2014)
  • Author(s): Ninomiya M, Kondo Y, Niihori T, Nagashima T, Kogure T, Kakazu E, Kimura O, Aoki Y, Matsubara Y, Shimosegawa T
  • Journal Title: Hepatol Res Volume: 44(6) Pages: 678-684
  • DOI: 10.1111/hepr.12168
  • Peer Reviewed
• [Journal Article] Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome (2013)
  • Author(s): Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, Takada F, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T, Nakayama K, Inoue S, Watanabe Y, Ogura T, Matsubara Y
  • Journal Title: Am J Hum Genet Volume: 93(1) Pages: 173-80
  • DOI: 10.1016/j.ajhg.2013.05.021.
  • Peer Reviewed
• [Journal Article] Exome sequencing identifies a novel TTN mutation in a family with hereditary myopathy with early respiratory failure (2013)
  • Author(s): Izumi R, Niihori T, Aoki Y, Suzuki N, Kato M, Warita H, Takahashi T, Tateyama M, Nagashima T, Funayama R, Abe K, Nakayama K, Aoki M, Matsubara Y
  • Journal Title: J Hum Genet Volume: 58(5) Pages: 259-66
  • DOI: 10.1038/jhg.2013.9
  • Peer Reviewed
• [Presentation] エクソームシークエンスによるNoonan症候群新規原因遺伝子RIT1の同定 (2013)
  • Author(s): 新堀哲也、青木洋子、番匠俊博、岡本伸彦、水野誠司、黒澤健司、緒方勤、高田史男、長谷川奉延、舟山亮、長嶋剛史、中山啓子、井上晋一、渡邊裕介、小椋利彦、松原洋一
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 20131120-23
• [Presentation] Myofibrillar myopathyの大家系における次世代型シークエンサーを用いた新たな原因遺伝子の同定 (2013)
  • Author(s): 井泉瑠美子、新堀哲也、青木洋子、鈴木直輝、加藤昌昭、割田仁、高橋俊明、竪山真規、長嶋剛史、舟山亮、阿部康二、中山啓子、青木正志、松原洋一
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 20131120-23
• [Presentation] エクソーム解析によりTBX1変異が同定された家族性の特徴的顔貌・鼻咽頭閉鎖不全・低Ca血症を呈する5例 (2013)
  • Author(s): 緒方勤、田中紀子、河井昌彦、深見真紀、新堀哲也、青木洋子、松原洋一
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 20131120-23
• [Presentation] A mutation in A-band titin is associated with hereditary myopathy with early respiratory failure in a Japanese family (2013)
  • Author(s): R. Izumi, T. Niihori, Y. Aoki, N. Suzuki, M. Kato, H. Warita, T. Takahashi, M. Tateyama, T. Nagashima, R. Funayama, K. Abe, K. Nakayama, M. Aoki, Y. Matsubara
  • Organizer: American Society of Human Genetics 63rd Annual Meeting
  • Place of Presentation: 米国・ボストン
  • Year and Date: 20131022-26
• [Presentation] Exome sequencing identifies mutations in a novel gene in patients with Noonan syndrome (2013)
  • Author(s): T. Niihori, Y. Aoki, T. Banjo, N. Okamoto, S. Mizuno, K. Kurosawa, T. Ogata, F. Takada, M. Yano, T. Ando, T. Hoshika, C. Barnett, H. Ohashi, H. Kawame, T. Hasegawa, T. Okutani, T. Nagashima, S. Hasegawa, R. Funayama, T. Nagashima, K. Nakayama, S. Inoue, Y. Watanabe, T. Ogura, Y. Matsubara
  • Organizer: American Society of Human Genetics 63rd Annual Meeting
  • Place of Presentation: 米国・ボストン
  • Year and Date: 20131022-26