RNF213 gene related intracranial findings and risk evaluation for moyamoya disease

• Project/Area Number: 15H04871
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Kure Shigeo 東北大学, 医学系研究科, 教授 (10205221)
• Co-Investigator(Kenkyū-buntansha): 冨永 悌二 東北大学, 医学系研究科, 教授 (00217548) ; 田邉 修 東北大学, 東北メディカル・メガバンク機構, 教授 (70221398)
• Co-Investigator(Renkei-kenkyūsha): TAKI YASUYUKI 東北大学, 加齢医学研究所, 教授 (10375115)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: もやもや病 / RNF213遺伝子変異 / 頭部MRI/MRA検査 / 東北メディカル・メガバンク / 頭部MRI / 遺伝子検査 / RNF213遺伝子 / 遺伝子多型 / 頭部MRI検査 / 発症リスク評価 / 一塩基多型 / 創始者変異 / SNPマイクロアレイ / 血中バイオマーカー / 発症リスク / 高頻度遺伝子変異 / 血清バイオマーカー

Outline of Final Research Achievements

Tohoku Medical Megabank has started screening program of brain MRI findings in its resident cohort.In this study we compered brain MRI/MRA findings of two participant groups that have the c.14576G>A-mutation or not, a Moyamoya disease related mutation in RNF213. Several findings specific to the mutation-positive group were identified. Volumes of various brain regions were measured, which were subject to statistical analysis for significant difference between the two groups.No metabolite has been identified to date, which plasma level differs significantly between the mutation-positive and negative groups.

Research Products

• [Journal Article] Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2,049 individuals (2018)
  • Author(s): Y Yamaguchi-Kabata, J Yasuda, O Tanabe, Y Suzuki, H Kawame, N Fuse, M Nagasaki, Y Kawai, K Kojima, F Katsuoka, S Saito, I Danjoh, I Motoike, R Yamashita, S Koshiba, D Saigusa, G Tamiya, S Kure, N Yaegashi, Y Kawaguchi, F Nagami, S Kuriyama, J Sugawara, N Minegishi, A Hozawa, T Takai-Igarashi, K Kinoshita, M Yamamoto.
  • Journal Title: Journal of Human Genetics. Volume: 63 Issue: 2 Pages: 213-230
  • DOI: 10.1038/s10038-017-0347-1
  • Peer Reviewed / Open Access
• [Journal Article] Evolution into moyamoya disease in an infant with internal carotid artery aneurysms (2017)
  • Author(s): Tanaka Ryosuke、Takahashi Satoru、Okano Satomi、Okayama Akie、Suzuki Nao、Kure Shigeo、Azuma Hiroshi
  • Journal Title: eNeurologicalSci Volume: 6 Pages: 80-82
  • DOI: 10.1016/j.ensci.2017.01.002
  • NAID: 120006337814
  • Peer Reviewed
• [Journal Article] Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease. (2016)
  • Author(s): Kanoke A, Fujimura M, Niizuma K, Fujimura T, Kakizaki A, Ito A, Sakata H, Sato-Maeda M, Kure S, Tominaga T.
  • Journal Title: Brain Res Volume: in press Pages: 1-9
  • DOI: 10.1016/j.brainres.2016.03.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease. (2015)
  • Author(s): Kanoke A, Fujimura M, Niizuma K, Ito A, Sakata H, Sato-Maeda M, Morita-Fujimura Y, Kure S, and Tominaga T.
  • Journal Title: Brain Res Volume: 1624 Pages: 497-505
  • DOI: 10.1016/j.brainres.2015.07.039
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Differing phenotypes of Moyamoya disease in a familial case involving heterozygous c.14429G > A variant in RNF213. (2015)
  • Author(s): Inoue T, Murakami N, Sakadume S, Kido Y, Kikuchi A, Ichinoi N, Suzuki K, Kure S, Sakuta R.
  • Journal Title: Pediatr Int. Volume: 57 Issue: 4 Pages: 798-801
  • DOI: 10.1111/ped.12689
  • Peer Reviewed
• [Journal Article] Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease. (2015)
  • Author(s): Ito A, Fujimura M, Niizuma K, Kanoke A, Sakata H, Morita-Fujimura Y, Kikuchi A, Kure S, Tominaga T.
  • Journal Title: Brain Res Volume: 16 Pages: 310-320
  • DOI: 10.1016/j.brainres.2014.11.014
  • Peer Reviewed
• [Book] Moyamoya Disease Explored through RNF213 (2017)
  • Author(s): Koizumi A, Nagata K, Houkin K, Tominaga T, Miyamoto S, Kure S, Tournier-Lasserve E
  • Total Pages: 185
  • Publisher: Springer
  • ISBN: 9789811027109
• [Book] Moyamoya disease explored through RNF213 (2017)
  • Author(s): Kure S (Edts, Koizumi A, Nagata K, Houkin K, Tominaga T, Miyamoto S, Kure S, Tourinier-Lasserve E)
  • Total Pages: 185
  • Publisher: Springer