Elucidate the pathophysiology of a novel syndrome caused by genes involving ATM signal pathway

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15907
• 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: Yokohama City University
• Principal Investigator: UCHIYAMA Yuri 横浜市立大学, 附属病院, 助教 (50829794)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ATM signaling pathway / 成長障害 / 発達障害 / 造血障害 / NGS解析

Outline of Final Research Achievements

In this study, RNA sequencing was performed to evaluate the functional changes of downstream genes caused by variants identified in two genes on the ATM signaling pathway, but there were no significant expression changes.
We conducted exome sequencing for 45 families with similar neurodevelopmental disorders with or without immunodeficiencies, focusing on genes on the ATM signaling pathway, and detected pathogenic variants causing neurodevelopmental disorders.
In addition, somatic variants of the UBA1 gene, strongly associated with the ATM signaling pathway, cause VEXAS syndrome. We established efficient detection methods for these variants and clarified the characteristics related to autoinflammation and hematopoietic disorders of VEXAS syndrome.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

原因不明の先天性疾患の遺伝学的病態が解明されることで、新たな治療法開拓にも大きくつながる。また、既知疾患の遺伝学的診断がなされることにより、今後の経過の予測や、治療方針の決定に寄与することができる。効率的なバリアント検出法の確立により、より簡便に、そして精度高く診断可能となり、非常に有意義である。