Identification of a novel gene causing genetic disorder of copper metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16853
• 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: Kyoto University
• Principal Investigator: Yoshida Takeshi 京都大学, 医学研究科, 助教 (50790557)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 銅代謝異常症 / 遺伝性疾患

Outline of Final Research Achievements

In a family with a hereditary copper deficiency different from any known disease, abnormality of CTR1 gene was identified. CTR1 is responsible for transporting copper into cells. Copper uptake in the patient's fibroblasts was diminished. To further analyze CTR1, we established a cell line without ATP7A, which exports copper outside of cells. Using the cell line, we demonstrated that CTR1 abnormality observed in the patients disturbed copper transport. In conclusion, this study revealed the possibility of an association between CTR1 and a novel hereditary copper deficiency.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

遺伝性銅代謝異常症は、ATP7A異常に伴うメンケス病とオクシピタールホーン症候群、ATP7B異常に伴うウィルソン病が知られているが、今回の研究により新たにCTR1異常が遺伝性銅代謝異常症に関与している可能性を示した。新規疾患の発見という点に加えて、銅トランスポーターCTR1の生体内での機能解明にも寄与するため、学術的意義が高いと考えられる。また、本研究がさらに発展すれば、銅代謝異常症の診断や治療に結びつく可能性があり、大きな社会的意義も期待できる。