Detection of novel causative genes and elucidation of the pathomechanisms of undiagnosed cases of inborn errors of immunity by whole exome sequencing analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20905
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University (2023); National Center for Global Health and Medicine (2022)
• Principal Investigator: Takada Sanami 東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト助教 (60733904)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 先天性免疫異常症 / 全エクソーム解析

Outline of Final Research Achievements

Inborn errors of immunity are rare diseases causing defects of immune systems by specific gene variants. It is required to detect the causing genes for early diagnosis and proper treatments. Still, a lot of cases of inborn errors of immunity remain undiagnosed, who requires detection of their causing genes.
In this study, we collected new 8 cases of inborn errors of immunity for analysis of whole exome sequencing and 121 cases for re-analysis. By whole exome sequencing analysis of new cases, we identified a variant of novel candidate causing gene. We studied the pathomechanism of the defect of immune system of the gene variant, which revealed the function abnormality of the gene variant carried by the patient.

Free Research Field

臨床免疫

Academic Significance and Societal Importance of the Research Achievements

これまで診断のついていなかった先天性免疫異常症患者の新たな原因遺伝子を同定し機能解析を行ったことは、免疫異常症のメカニズムの解明や、ヒトが病原体から身を守る免疫機構の解明に大きく寄与すると考えられた。また今後は、まだ診断がついていないが同じ原因遺伝子変異をもつ他の患者の診断や、将来的な治療法開発へとつながる成果であり、患者への還元につながり社会に貢献する研究成果であった。