Biochemical characteristics of erythrocytes in extremely preterm infants and identification of loci conferring susceptibility to prolonged severe hyperbilirubinemia
| Project/Area Number |
20K08239
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
菅野 仁 東京女子医科大学, 医学部, 特任教授 (70221207)
谷ヶ崎 博 日本大学, 医学部, 准教授 (90378141)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 赤血球 / 遷延性重症黄疸 / 臍帯血 / 新生児 / 成人 / 早産児 / 超早産児 / 黄疸 / 感受性遺伝子 |
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| Outline of Research at the Start |
新生児黄疸の治療法は確立しているにも関わらず、超早産児の慢性ビリルビン脳症患者が年々増え続けている。我々は遷延性重症黄疸がその発症要因となっていることを突き止めた。遷延性重症黄疸の発症予測マーカーがわかれば、黄疸の重症化前に治療に繋げることができる。本研究の目的は、最新の赤血球特殊検査と網羅的遺伝子解析技術を用いて、超早産児の赤血球の特徴や遺伝学的背景の違いから遷延性重症黄疸の発症予測マーカーを開発することである。
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| Outline of Final Research Achievements |
Values of flow cytometric osmotic fragility (FCM-OF) and Eosin 5'-Maleimide (EMA) binding capacity of erythrocytes in cord blood (CB) were measured to generate reference values and compared with those of erythrocytes in adult blood (AP). To identify genes associated with prolonged severe hyperbilirubinemia, a next-generation sequencing panel of 63 target genes was evaluated in infants with congenital hemolytic anemia. There were significant differences in FCM-OF and EMA measurements between CB and AP. The reference values for CB were established. Next-generation sequencing analysis revealed that among children with spontaneous remission of hemolytic anemia by 1 year of age, there were those with variant of uncertain significance in PIEZO1.
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| Academic Significance and Societal Importance of the Research Achievements |
古くから「特発性新生児黄疸」という疾患名が定着し、新生児の黄疸は原因が不明であることが一般的になっている。また、赤血球関連特殊検査の多くの項目に新生児の基準値がなかった。本研究で初めて、臍帯血の赤血球関連特殊検査のflow cytometric osmotic fragility（FCM-OF）およびEosin 5’-Maleimide（EMA）結合能の基準値を作成できた。PIEZO1の変異が一過性の溶血により重症の新生児黄疸を引き起こす可能性があることを明らかにし、原因不明だった重症新生児黄疸の原因や病態解明ができた。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis.2023
Author(s)
Nakahara E, Shimojima Yamamoto K, Ogura H, Aoki T , Utsugisawa T, Azuma K, Akagawa H, Watanabe K, Muraoka M, Nakamura F, Kamei M, Tatebayashi K, Shinozuka J, Yamane T, Hibino M, Katsura Y, Nakano-Akamatsu S, Kadowaki N, Maru Y, Etsuro Ito E, Ohga S, Yagasaki H, Morioka I, Yamamoto T and Kanno H.
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Journal Title
Hum Genome Var
Volume: 10
Issue: 1
Pages: 8-8
DOI
Related Report
Peer Reviewed / Open Access
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