Elucidation of the molecular basis of osteogenesis imperfecta and novel therapy through activation of Wnt signaling and OASIS

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K07869
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tohoku University
• Principal Investigator: KANNO Junko 東北大学, 大学病院, 講師 (30509386)
• Co-Investigator(Kenkyū-buntansha): 藤原 幾磨 東北大学, 医学系研究科, 非常勤講師 (10271909) ; 新堀 哲也 東北大学, 医学系研究科, 准教授 (40436134) ; 鈴木 大 東北大学, 大学病院, 助教 (70814713)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 骨形成不全症 / PPIB / SERPINEF1

Outline of Final Research Achievements

Exome analysis was performed on six patients, including two patients in whom no mutations were identified in the responsible genes, COL1A1 and COL1A2, in a previous study, a comprehensive mutation analysis of osteogenesis imperfecta, and four new patients. After exome analysis, the mutations detected were confirmed by the Sanger method. Exome analysis identified COL1A2 mutations in two families.COL1A2 mutation was identified in one family and PPIB mutation was identified in one family. This is the first case of osteogenesis imperfecta caused by PPIB mutation in Japan. In the final year of the study, a patient with SERPINEF1 mutation was also identified, the first case of SERPINEF1 mutation osteogenesis imperfecta in Japan.

Free Research Field

小児内分泌学

Academic Significance and Societal Importance of the Research Achievements

骨形成患者の包括的な解析結果は、エクソーム解析でも、これまでの報告で原因として同定されていたCOL1A1、COL1A2においては過去の報告と同様の検出率であった。また、本邦初のPPIB変異とSERPINEF1 変異を同定し、稀ではあるが、本邦においてもCOL1A1、COL1A2以外が病院の骨形成不全の患者の存在が証明された。