Molecular genetic analysis of familial inclusion body myositis

• Project/Area Number: 18K15440
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kubota Akatsuki 東京大学, 医学部附属病院, 助教 (30771589)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 封入体筋炎 / 遺伝子 / 連鎖解析

Outline of Final Research Achievements

Inclusion body myositis (IBM) is a rare sporadic inflammatory myopathy and usually is not inherited. However, we found a family with two patients with IBM and hypothesized that a genetic factor might cause IBM in the family. DNA samples of the family members were extracted from peripheral white blood cells after written informed consents were obtained. Linkage analysis showed an elevated LOD score of approximately 1 in a wide range of X chromosome. Haplotype analysis showed that a region of 1.1Mb in Xp22 was shared only in patients. Whole-exome sequencing showed no rare variants in the shared region.

Academic Significance and Societal Importance of the Research Achievements

封入体筋炎は病態不明の炎症性筋疾患で、現時点では治療法は存在しない。本研究では家族性封入体筋炎の遺伝子解析を通じて病態解明を試みた。家系の情報からX染色体潜性遺伝が考えられたがエクソン領域に稀な変異は認めなかったことから、今後はイントロン領域の解析が検討される。更なる遺伝的検討により封入体筋炎の病態解明が期待される。

Research Products

• [Journal Article] Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy (2022)
  • Author(s): Akatsuki Kubota, Jun Shimizu, Atsushi Unuma, Meiko Maeda, Yuichiro Shirota, Masato Kadoya, Naohiro Uchio, Yoshio Sakiyama, Noritoshi Arai, Yasushi Shiio, Yoshikazu Uesaka, Hideji Hashida, Nobue K Iwata, Jun Goto, Ran Nakashima, Tsuneyo Mimori, Tatsushi Toda
  • Journal Title: Neuromuscular Disorders Volume: 32(1) Issue: 1 Pages: 25-32
  • DOI: 10.1016/j.nmd.2021.10.007
  • Peer Reviewed / Open Access
• [Journal Article] DMD exon 2 duplication due to a complex genomic rearrangement is associated with a somatic mosaicism (2022)
  • Author(s): Akatsuki Kubota, Hiroyuki Ishiura, Kristine Joyce Linay Porto, Masaki Tanaka, Jun Mitsui, Atsushi Unuma, Hisataka Maki, Issei Komuro, Shoji Tsuji, Jun Shimizu, Tatsushi Toda
  • Journal Title: Neuromuscular Disorders Volume: 32(3) Issue: 3 Pages: 263-269
  • DOI: 10.1016/j.nmd.2021.12.004
  • Peer Reviewed / Open Access
• [Presentation] HMGCRミオパチーではALTが優位に上昇する (2022)
  • Author(s): 久保田暁、清水潤、鵜沼敦、前田明子、代田悠一郎、角谷真人、中嶋蘭、三森経世、戸田達史
  • Organizer: 第63回日本神経学会総会
  • Int'l Joint Research
• [Presentation] Application of droplet digital PCR for detection of somatic mosaicism in dystrophinopathy. (2021)
  • Author(s): Akatsuki Kubota, Hiroyuki Ishiura, Kristine Joyce Linay Porto, Masaki Tanaka, Atsushi Unuma, Shoji Tsuji, Jun Shimizu, Tatsushi Toda
  • Organizer: 第62回日本神経学会総会
  • Int'l Joint Research
• [Presentation] Clinical description of familial inclusion body myositis and molecular genetic analysis. (2019)
  • Author(s): Akatsuki Kubota, Hiroyuki Ishiura, Jun Mitsui, Jun Shimizu, Shoji Tsuji, Tatsushi Toda
  • Organizer: 3rd Global Conference on Myositis 2019
  • Int'l Joint Research