Exome analysis identifed a molecular origin of primary immunodeficiency

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05356
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: MINEGISHI Yoshiyuki 徳島大学, 先端酵素学研究所(プロテオ), 教授 (10343154)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫不全症 / アレルギー

Outline of Final Research Achievements

Human primary immunodeficiency is characterized by immunodeficiency, allergy, and cancer, which is caused by a mutation in a gene expressed in immune systems. We identified hyper-IgE syndrome is caused by dominant negative mutations of the STAT3 gene. We still do not know the molecular origins of 30 percent of hyper-IgE syndrome patients. To identify a novel molecular origin of hyper-IgE syndrome, we performed exome analysis of 100 hyper-IgE patients without mutations in the known molecular origins of hyper-IgE syndrome. We extensively performed in silico, in vitro, and in vivo analysis and identified novel causing gene of hyper-IgE syndrome.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

高IgE症候群は、単一遺伝子の異常により黄色ブドウ球菌感染症、骨粗鬆症、アトピー性皮膚炎、高IgE血症などの臨床的に重要で頻度の高い疾患を呈する。そのため、高IgE症候群の新規原因遺伝子の同定は、高IgE症候群の早期診断、予後の予測、治療法選択に貢献するだけでなく、黄色ブドウ球菌感染症、骨粗鬆症・アトピー性皮膚炎などの一般的な疾患の新規診断法、治療法・予防法の発見に結び付く可能性があるため、高IgE症候群新規原因遺伝子の発見は、学術的意義・社会的意義共に大きい。