Identification of novel genes responsible for congenital portosystemic venous shunt

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyushu University
• Principal Investigator: Ishii Kanako 九州大学, 大学病院, 特任講師 (90400332)
• Co-Investigator(Kenkyū-buntansha): 酒井 康成 九州大学, 医学研究院, 准教授 (10380396) ; 内海 健 九州大学, 医学研究院, 教授 (80253798)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 先天性門脈体循環短絡症 / 全エクソーム解析 / 肺高血圧

Outline of Final Research Achievements

Congenital portosystemic venous shunt (CPSVS) is a rare disease defined as shunt vessels between the portal and systemic vein, which results in ominous complications including pulmonary arterial hypertension (PAH), hepatic encephalopathy and liver tumors. Whole exosome analysis was performed on 13 CPSVS patients to identify novel genes responsible for CPSVS. No genetic abnormality common in all patients was identified. No mutations were found in the AHR, AIP, and ARNT genes that have been reported as causative genes of patent ductus venosus in mice. On the other hand, heterozygous mutations were identified in genes　responsible for another disease in most CPSVS patients.

Free Research Field

小児内分泌

Academic Significance and Societal Importance of the Research Achievements

CPSVSは致死的な合併症を起こす重篤な疾患である一方、稀少疾患であるため情報が少ない。臨床経過と治療効果をまとめた発表論文の掲載は、本疾患の存在を広く認知させ、シャント閉鎖を含む治療方針決定の一助になった。また、これまでCPSVSの遺伝子変異解析を行った報告はなく、本研究が世界初である。遺伝子型と表現型（合併症、自然歴、予後）との関連性を解明することで、患者マネージメントのさらなる向上が期待できる。また本研究の遺伝学的知見は、早期診断マーカーの開発、遺伝子治療を目指すトランスレーショナル研究の基盤構築に貢献できる。