Comprehensive genetic analysis of unclassified Inherited bone marrow failure syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16887
• 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: Nagoya City University (2022); Nagoya University (2020-2021)
• Principal Investigator: Hamada Motoharu 名古屋市立大学, 医薬学総合研究院(医学), 講師 (60845171)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 遺伝性骨髄不全症候群 / 全エクソン解析 / AMeD症候群

Outline of Final Research Achievements

Inherited bone marrow failure syndrome (IBMFS) is an inherited disorder with a poor prognosis, but in over half of cases the causative gene is unknown. In this study of IBMFS with unknown causative genes, a comprehensive genetic analysis (whole exon analysis) of patients and their parents was performed to identify the causative gene and obtain a genetic diagnosis, as well as to identify new causative genes. Thirty-seven families were analyzed, and in 11 cases (28%) the causative gene could be identified. One of these cases was diagnosed with AMeD syndrome, a new form of IBMFS. This study suggests the importance of genetic analysis of IBMFS and contributes to understanding the pathogenesis of the disease.

Free Research Field

遺伝性骨髄不全症候群

Academic Significance and Societal Importance of the Research Achievements

本研究により、疾患の発端者（患者）のみでなく両親の遺伝子解析を行うことで、IBMFSの遺伝子診断効率が向上することが示された。遺伝子パネル検査や発端者の網羅的遺伝子解析でも原因遺伝子が特定されない場合は、両親検体の解析を積極的に検討することが重要である。これにより、正確な遺伝子診断に基づく適切な医療的介入が可能となる。また、遺伝性骨髄不全症候群の新たな病型であるAMeD症候群の発見により、IBMFSの原因となる新たな病態が解明された。