Analysis to reveal a disease causing gene in a family with hereditary myopathy with inclusion body

• Project/Area Number: 24659421
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: AOKI Masashi 東北大学, 医学(系)研究科(研究院), 教授 (70302148)
• Co-Investigator(Kenkyū-buntansha): KATO Masaaki 東北大学, 病院, 助教 (50622479)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 1 C 臨床神経分子遺伝学 / 筋萎縮 / 筋疾患 / CytoplasmicBodyMyopathy / 次世代シークエンサー / プロテアソーム / 封入体を伴う筋疾患

Research Abstract

Myofibrillar myopathy (MFM) is a group of chronic muscular disorders that show the focal dissolution of myofibrils and accumulation of degradation products. In this study, we performed linkage analysis and exome sequencing on the family of MFM patients and identified a novel c.90263G4T mutation in the TTN gene (NM_001256850). Mutations in TTN in patients with hereditary myopathy with early respiratory failure (HMERF, MIM #603689) was reported very recently. The mutation identified in this study is located on the A-band domain of titin, suggesting a strong relationship between mutations in the A-band domain of titin and HMERF. It is possible that focused analysis of TTN may detect more mutations in patients with MFMs, especially in those with early respiratory failure.

Research Products

• [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) Issue: 5 Pages: 259-66
  • DOI: 10.1038/jhg.2013.9
  • NAID: 10031177220
  • Peer Reviewed
• [Journal Article] Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. (2013)
  • Author(s): Takahashi T, Kokubo Y.
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 71(7) Issue: 4 Pages: 433-440
  • DOI: 10.1136/jnnp-2011-301339
  • 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
  • NAID: 10031177220
  • Peer Reviewed
• [Journal Article] Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B (2013)
  • Author(s): Takahashi T,Aoki M, Suzuki N,Tateyama M, aginuma C,Sato H, Hayasaka M, Sugawara H,Ito M,Abe-Kondo E,Shimakura N,Ibi T,Kuru S,Wakayama T,Sobue G,Fujii N,Saito T, Matsumura T,Funakawa I,Mukai E,Kawanami T,Morita M,Yamazaki M,Hasegawa T, Shimizu J,Tsuji S, Kuzuhara S,Tanaka H,Yoshioka M,Konno H,Onodera H,Itoyama Y
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 84(4) Pages: 433-40
  • Peer Reviewed
• [Presentation] A mutation in A-band titin is associated with hereditary myopathy with early respiratory failure in a Japanese family (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.
  • Organizer: the 63rd Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Boston, MA,USA
  • Year and Date: 2013-10-24
• [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原因遺伝子の同定 (2013)
  • Author(s): 井泉瑠美子,鈴木直輝,加藤昌昭,割田仁,高橋俊明,竪山真規,新堀哲也,青木洋子,松原洋一,舟山亮,西田有一郎,長嶋剛史,中山啓子,青木正志
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-29
• [Presentation] A mutation in A-band titin is associated with hereditary myopathy with early respiratory failure in a Japanese family. (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
  • Organizer: the 63rd Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Boston,USA