Establishment of comprehensive genetic analysis and proposal of novel disease entities in inherited thrombocytopenias.
| Project/Area Number |
19K08855
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Sasahara Yoji 東北大学, 医学系研究科, 准教授 (60372314)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 遺伝性血小板減少症 / 網羅的遺伝子解析 / MECOM / CDC42 |
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| Outline of Research at the Start |
小児期の血小板減少症には、免疫性血小板減少性紫斑病（ITP）の他に、血小板産生を制御する遺伝子群の変異を病因とする遺伝性血小板減少症がある。本研究では、研究代表者のWiskott-Aldrich症候群の分子病態および遺伝性血小板減少症における新規原因遺伝子解析の研究基盤を発展させるため、以下の研究を行う。
１．遺伝性血小板減少症の既知原因遺伝子の網羅的遺伝子診断系の確立と臨床への還元
２．既知遺伝子が正常である臨床検体を用いた新規原因遺伝子の探索
３．新規原因遺伝子MECOMの異常による疾患概念の確立とマウスモデルの病態解析
４．新規原因遺伝子CDC42の異常による疾患概念の確立と細胞レベルの病態解析
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| 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.
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| 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。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation2022
Author(s)
Nishitani-Isa M, Mukai K, Honda Y, Nihira H, Tanaka T, Shibata H, Miyamoto T, Komada K, Hiejima E, Izawa K, Kawasaki Y, Osawa M, Katata Y, Onodera S, Watanabe T, Kure S, Takita J, Ohara O, Saito M, Nishikomori R, Taguchi T, Sasahara Y#, Yasuki T#. (# Equal corresponding author)
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Journal Title
J Exp Med
Volume: 219(6)
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Phenotypic heterogeneity in individuals with MECOM variants in 2 families.2022
Author(s)
Niihori T, Tanoshima R, Sasahara Y, Sato A, Irie M, Saito-Nanjo Y, Funayama R, Shirota M, Abe T, Okuyama Y, Ishii N, Nakayama K, Kure S, Imaizumi M, Aoki Y.
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Journal Title
Blood Adv.
Volume: -
Issue: 18
Pages: 5257-5261
DOI
Related Report
Peer Reviewed / Open Access
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