Development of novel diagnostic method for refractory pediatric liver diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19391
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Hayashi Hisamitsu 東京大学, 大学院薬学系研究科(薬学部), 助教 (10451858)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 小児遺伝性肝疾患 / 診断 / マクロファージ / 表現型解析

Outline of Final Research Achievements

In the pediatric hereditary liver diseases, a definitive diagnosis of each disease is made by clinical findings followed by genomic analysis. However, there are some cases in which it is difficult to distinguish from similar diseases due to inability to identify the mutation or to distinguish between the pathogenic mutation and the rare normal variant. In order to solve this situation, this study developed a diagnostic method based on gene function analysis. Peripheral blood monocytes from the patients were differentiated into macrophages and subjected to various analysis. Abnormal phenotypes that could contribute to discriminate the pediatric hereditary liver diseases was identified.

Free Research Field

小児肝臓病学

Academic Significance and Societal Importance of the Research Achievements

小児遺伝性肝疾患群では、臨床診断の後、遺伝子検査を経て確定診断に至ります。しかしながら変異を同定できない、あるいは病因変異とrare normal variantの区別が出来ない等の理由により、遺伝子検査では類似疾患との鑑別に難渋し、確定診断に至らない症例が散見されます。本研究では、当該疾患患児の末梢血単球を活用し、疾患鑑別に資する複数の表現型異常を同定しました。