Establishment of comprehensive genetic analysis and proposal of novel disease entities in inherited thrombocytopenias.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tohoku University
• Principal Investigator: Sasahara Yoji 東北大学, 医学系研究科, 准教授 (60372314)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 遺伝性血小板減少症 / 網羅的遺伝子解析 / MECOM / CDC42

Outline of Final Research Achievements

Childhood thrombocytopenias include inherited thrombocytopenias caused by mutations in responsible genes that control platelet production, besides immune thrombocytopenia. In this research project, I performed four projects described below to promote basic research and clinical applications on Wiskott-Aldrich syndrome and its related disorders.
(1) Establishment of comprehensive genetic analysis for inherited thrombocytopenias and its clinical application. (2) Search for novel responsible genes for inherited thrombocytopenias in clinical samples. (3) Establishment of novel disease entitiy of MECOM-associated syndrome and analysis of mice model of the disease. (4) Establishment of novel disease entity of CDC42 C-term disease and molecular and cellular analysis of the disease.

Free Research Field

小児血液・腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、これまでの研究代表者の研究業績を基盤として、免疫性血小板減少性紫斑病（ITP）との鑑別診断が必要な遺伝性血小板減少症全体の系統的かつ網羅的遺伝子診断系を確立して臨床に還元したこと、未知原因遺伝子の多い本疾患群において新規原因遺伝子を探索し候補遺伝子を同定したこと、かつ世界に先駆けて提唱する2つの新規疾患概念として、MECOM異常症およびCDC42異常症の確立と分子病態の解明に発展させた。以上の成果は、小に血液・腫瘍学における造血や巨核球・血小板産生機構の研究分野において、臨床的還元を行ったことに加えて、新規2疾患の提唱を行ったことに学術的意義と社会的意義があった。