A mutation analysis of complement-related genes in transplant-associated thrombotic microangiopathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15679
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Miyazaki
• Principal Investigator: YAMADA AI 宮崎大学, 医学部, 助教 (90816688)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 移植関連血栓性微小血管障害 / 造血幹細胞移植(HSCT) / TA-TMA疾患パネル / ターゲットシーケンスキャプチャー法 / 次世代シーケンサー / 低頻度バリアント

Outline of Final Research Achievements

We planned to analyze 40 genes, including 17 genes, that are known to be involved in the etiology of transplant-associated thrombotic microangiopathy (TA-TMA) in American adults, in order to identify the causative variants of TA-TMA in Japanese children. We collaborated with Kindai University, Yokohama City University Graduate School of Medicine, and Kagoshima University to analyze a large number of samples. After receiving approval from all institutional review boards, we performed exome sequencing for 20 cases with TA-TMA and 20 cases without TA-TMA. Several low-frequency variants (e.g.,CFHR5, CFHR4, THBD, and C1RL) were found in patients with TA-TMA; however, more samples would be analyzed in order to determine whether these variants are significant.

Free Research Field

小児血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

小児の血液腫瘍領域において造血幹細胞移植は大きく予後改善に貢献してきた。一方、予期せぬ致死的合併症が生じることがあるが、TA-TMAは代表的合併症の1つである。TA-TMA発症には何らかの素因を有している患者に、大量化学療法をはじめとする様々なストレス下で血管内皮障害が生じることが端緒と考えられている。TA-TMAの病因となりうる遺伝子バリアントが同定されれば、移植前にスクリーニングを行うことにより予防が可能となり、将来的に造血幹細胞移植を行う患者たちに多くの恩恵が与えられると期待できる。