Pathophysiological Study on Aortopathy towards Prevention

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: MORISAKI TAKAYUKI 東京大学, 大学院新領域創成科学研究科, 特任教授 (30174410)
• Co-Investigator(Kenkyū-buntansha): 森崎 裕子 公益財団法人榊原記念財団(臨床研究施設・研究部門), 臨床遺伝科医局, 科長 (40311451) ; 小原 收 公益財団法人かずさDNA研究所, その他部局等, 副所長 (20370926) ; 藤木 亮次 公益財団法人かずさDNA研究所, ゲノム事業推進部, 特任研究員 (40534516)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 病因遺伝子 / 循環器 / 遺伝性疾患 / 病態解析 / 大動脈

Outline of Final Research Achievements

Recent study revealed numbers of pathogenic genes for hereditary aortic diseases. However, many patients with these diseases due to unknown genetic cause had not been diagnosed or properly managed. This study aimed to improve genetic test and precise classification of aortic diseases, improving better medical care for them. We performed exome analysis of young patients including 43 cases with past history of aortic diseases as well as undiagnosed 304 cases with aortic diseases. As a result, we identified PMEPA1 gene as a new pathogenic gene for hereditary aortopathy by an international collaborative study with other researchers. Furthermore, we identified more aortic patients with PMEPA1 gene variants. Genetic and phenotypic study of these patients revealed characteristics of patients with this particular gene mutation. These results will help better medical care and prevention of aortic diseases.

Free Research Field

循環器遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究では、遺伝性動脈疾患の新規病因遺伝子PMEPA1が同定され、国内外の研究者との連携により、PMEPA1変異症例の表現型の検討が進んだ。既知遺伝子変異を有する遺伝性動脈疾患との表現型比較も進めることができ、遺伝性動脈疾患患者について、より高精度な診断にむけての学術基盤と情報基盤を整えることができた。結果として遺伝性動脈疾患の診断、治療につながる知見が明らかとなり、致死的な疾患イベントにつながりやすい大動脈疾患の克服にむけた成果につなげることができ、診療の高度化が可能となり、社会的意義は大きい。