Elucidation of mechanism for short stature with abnormal GH-IGF signaling

• Project/Area Number: 17K10078
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tottori University
• Principal Investigator: KAWASHIMA YUKI 鳥取大学, 医学部, 講師 (20403412)
• Co-Investigator(Kenkyū-buntansha): 伯野 史彦 東京大学, 大学院農学生命科学研究科(農学部), 助教 (30282700)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小児内分泌学 / 成長障害 / GH-IGFシグナル / IGF1R / GH-IGF系経路 / 遺伝子 / 小児科学 / 内分泌学

Outline of Final Research Achievements

Targeted resequencing using TruSight One sequencing panels and direct PCR
sequencing were performed in　18 patients with unknown short stature. We
identified a heterozygous IGF1R mutation (p.Tyr 888 X) in two patients. The mutation result in defecit of the expression of IGF1R protein in transiently transfected cells.

Academic Significance and Societal Importance of the Research Achievements

新たに2例のIGF1R遺伝子変異による成長障害を同定した。これまでの研究ではGH-IGFシグナル異常による成長障害は非常に稀とされているが、ある程度の割合で存在することが明らかになった。

Research Products

• [Journal Article] IGF2 Mutations (2019)
  • Author(s): Masunaga Yohei、Inoue Takanobu、Yamoto Kaori、Fujisawa Yasuko、Sato Yasuhiro、Kawashima-Sonoyama Yuki、Morisada Naoya、Iijima Kazumoto、Ohata Yasuhisa、Namba Noriyuki、Suzumura Hiroshi、Kuribayashi Ryota、Yamaguchi Yu、Yoshihashi Hiroshi、Fukami Maki、Saitsu Hirotomo、Kagami Masayo、Ogata Tsutomu
  • Journal Title: The Journal of Clinical Endocrinology & Metabolism Volume: 105 Issue: 1 Pages: 116-125
  • DOI: 10.1210/clinem/dgz034
  • Peer Reviewed / Open Access
• [Journal Article] Increased IRS2 mRNA Expression in SGA Neonates: PCR Analysis of Insulin/IGF Signaling in Cord Blood (2017)
  • Author(s): Fujimoto M, Sonoyama YK, Fukushima K, Imamoto A, Miyahara F, Miyahara N, Nishimura R, Yamada Y, Miura M, Adachi K, Nanba E, Hanaki K, Kanzaki S.
  • Journal Title: J Endocr Soc Volume: 1 Issue: 12 Pages: 1408-1416
  • DOI: 10.1210/js.2017-00294
  • Peer Reviewed / Open Access
• [Presentation] IRS1遺伝子変異（p.Ser685_Ser686del）は、IGF作用のみに影響を与え、成長障害を引き起こす (2019)
  • Author(s): 鞁嶋有紀 伯野史彦 妹尾慎太郎 山口由起子 西村玲 花木啓一 高橋伸一郎 神﨑晋
  • Organizer: 第53回日本小児内分泌学会学術集会