Clinical and molecular genetic study of elucidation of a cause of Moebius syndrome

• Project/Area Number: 15K09607
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kawasaki University of Medical Welfare
• Principal Investigator: MASUNO Mitsuo 川崎医療福祉大学, 医療福祉学部, 教授 (00389024)
• Co-Investigator(Kenkyū-buntansha): 黒澤 健司 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 部門長 (20277031)
• Co-Investigator(Renkei-kenkyūsha): AIDA Noriko 神奈川県立こども医療センター, 放射線科, 部長 (20586292) ; MATSUI Kiyoshi 神奈川県立こども医療センター, 総合診療科, 部長 (30601984)
• Research Collaborator: FUJII Yuta 神奈川県立こども医療センター, 放射線科, 医長
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: メビウス症候群 / ゲノム解析 / 病因

Outline of Final Research Achievements

1. Identification of an incomplete form of Moebius syndrome: We present 4 patients with an incomplete form of Moebius syndrome, characterized by congenital bilateral facial nerve paralysis and other cranial nerves involvements without abducens nerve paralysis.　Cranial MRI of the patients showed hypoplasia of the brainstem and facial nerves but normal abducens nerves.
2. Genomic analyses on the patients with Moebius syndrome: Whole exome sequencing analyses were performed on 9 patients with typical Moebius syndrome, 2 patients with an incomplete form of Moebius syndrome, and 5 patients with atypical Moebius syndrome. No candidate gene responsible for Moebius syndrome has been identified. Medical exome sequencing analyses performed on 2 patients with atypical Moebius syndrome revealed a de novo known TUBB3 mutation and a de novo novel CHD7 mutation, respectively.

Research Products

• [Presentation] Clinical and neuroimaging findings of an incomplete form of Moebius syndrome (2016)
  • Author(s): Mitsuo Masuno, Kiyoshi Matsui, Koji Tanoue, Noriko Aida, Yuta Fujii, Makiko Ohyama, Jun Shibasaki, Yasuko Yamanouchi, Kenji Kurosawa
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都府京都市左京区宝ヶ池）
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] Clinical and neuroimaging findings of an incomplete form of Moebius syndrome (2016)
  • Author(s): Mitsuo Masuno, Kiyoshi Matsui, Koji Tanoue, Noriko Aida, Yuta Fujii, Makiko Ohyama, Jun Shibasaki, Yasuko Yamanouchi, Kenji Kurosawa
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: Kyoto International Conference Center, Japan
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] Brain imaging analysis in Moebius syndrome (2015)
  • Author(s): Yuta Fujii, Noriko Aida, Kumiko Nozawa, Mikako Enokizono, Kiyoshi Matsui, Mitsuo Masuno, Tomio Inoue
  • Organizer: The 15th Annual Meeting of Asian & Oceanic Society for Pediatric Radiology
  • Place of Presentation: THE GRAND HALL Shinagawa Grand Central Tower 3F, Japan
  • Year and Date: 2015-06-12
  • Int'l Joint Research