Development of diagnostic screening method and treatment for asparagine synthetase deficiency

• Project/Area Number: 16K19637
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Kubota Kazuo 岐阜大学, 医学部附属病院, 助教 (10526940)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アスパラギン合成酵素欠損症 / アスパラギン合成酵素 / 遺伝学

Outline of Final Research Achievements

The aim of this study was to develop diagnostic screening method and treatment for asparagine synthetase deficiency. Expression experiment was performed using mutant expression vectors of four novel ASNS mutations we identified. In the stability analysis, there were no significant differences between mutants of ASNS protein and the wild type. We could not quantify of asparagine because of interrupting by endogenous proteins including cultured cells. There is markedly reduced proliferation of patient fibroblasts when cultured in growth medium without asparagine, compared to control fibroblasts. On the other hand, the fibroblasts were increased in medium including asparagine. The results suggest that asparagine supplementation may be effective in asparagine synthetase deficiency.

Research Products

• [Journal Article] The first report of Japanese patients with asparagine synthetase deficiency (2017)
  • Author(s): Yamamoto T, Endo W, Ohnishi H, Kubota K, Kawamoto N, Inui T, Imamura A, Takanashi JI, Shiina M, Saitsu H, Ogata K, Matsumoto N, Haginoya K, Fukao T
  • Journal Title: Brain Development Volume: 39 Issue: 3 Pages: 236-242
  • DOI: 10.1016/j.braindev.2016.09.010
  • Peer Reviewed
• [Presentation] Asparagine Synthetase Deficiency: The First Japanese Case Report and Review of Literature. (2017)
  • Author(s): Yamamoto T., Endo W., Ohnishi H., Kubota K., Kawamoto N., Inui T., Imamura A., Takanashi J. I., Shiina M., Saitsu H., Ogata K., Matsumoto N., Haginoya K., Fukao T.
  • Organizer: AOCCN2017 (14th Asia Oceanian Congress Child Neurology)
  • Int'l Joint Research
• [Presentation] 進行性の小頭症、重度の精神運動発達遅滞と難治性てんかんを認めアスパラギン合成酵素欠損症と診断した一例 (2016)
  • Author(s): 久保田 一生, 山本 崇裕, 川本 典生, 大西 秀典, 今村 淳, 才津 浩智, 松本 直通, 深尾 敏幸
  • Organizer: 第58回日本先天代謝異常学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-27
• [Presentation] Whole-exome解析により診断したアスパラギン合成酵素欠損症の変異機能解析 (2016)
  • Author(s): 山本 崇裕, 大西 秀典, 久保田 一生, 西村 紗織, 笠原 由貴子, 折居 建治, 今村 淳, 才津 浩智, 松本 直通, 深尾 敏幸
  • Organizer: 第58回日本小児神経学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-03