Identification of novel diseases with proteasome deficiency and their pathomechanism by analyzing a panel of associated genes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09780
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Wakayama Medical University
• Principal Investigator: Kanazawa Nobuo 和歌山県立医科大学, 医学部, 准教授 (90343227)
• Co-Investigator(Kenkyū-buntansha): 稲葉 豊 和歌山県立医科大学, 医学部, 助教 (00647571) ; 国本 佳代 和歌山県立医科大学, 医学部, 助教 (10438278)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: プロテアソーム / 自己炎症性疾患 / インターフェロン

Outline of Final Research Achievements

Cases who were clinically diagnosed as Nakajo-Nishimura syndrome but not associated with a PSMB8 mutation were collected from all over Japan and provided for analysis of a panel of proteasome-associated genes as well as the genes associated with known interferonopathy, inflammasome and autophagy, and/or for the whole exome sequencing. As a result, several cases with Aicardi-Goutieres syndrome harboring a TREX1 mutation were identified, as well as a case with a novel proteasome-associated autoinflammatory syndrome with a PSMB9 mutation and a case with a novel interferonopathy harboring a mutation in the gene whose role as a disease cause had not been reported. Analysis of the proteasome activities, formation of the proteasome complex and accumulation of ubiquitin in these cases suggested the presence of a pathomechanism distinct from that of Nakajo-Nishimura syndrome.

Free Research Field

皮膚炎症免疫学