Establishment of novel non-invasive diagnostic methods for mitochondrial cardiomyopathy
Project/Area Number |
20K08497
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Juntendo University |
Principal Investigator |
OKAZAKI ATSUKO 順天堂大学, 大学院医学研究科, 准教授 (70761691)
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Co-Investigator(Kenkyū-buntansha) |
山崎 悟 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (70348796)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | ミトコンドリア病 / 心筋症 / ミトコンドリア心筋症 / ヘテロプラスミー / ヘテロプラスミー率 / ミトコンドリアDNA / 遺伝性心筋症 / 非侵襲的診断法 / digital PCR / 変異ミトコンドリアDNA率(ヘテロプラスミー率) |
Outline of Research at the Start |
ミトコンドリア心筋症の診断が困難な一因として、変異ミトコンドリアDNAは主に心筋に存在するため診断には心筋組織が必要であることが挙げられる。申請者らはミトコンドリア心筋症例の各組織中で、尿検体が心筋の変異ミトコンドリアDNA率と良く相関する事実を発見した。申請者らは891例の自験データに基づく変異ミトコンドリアDNA定量化システムを開発し、132例のミトコンドリア病患者での検証に成功した。本研究では新規開発した変異ミトコンドリアDNA定量化システムを発展させて心筋症に最適化した変異定量化システムを開発し、非侵襲的に入手可能な尿検体を用いたミトコンドリア心筋症の新規診断法の確立を目的とする。
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Outline of Final Research Achievements |
We successfully established novel non-invasive diagnostic methods for mitochondrial cardiomyopathy. Firstly we completed dataset where we compared heteroplasmy in urine with that in heart tissue in several mitochondrial cardiomyopathy patients. Secondly, by using those dataset, we developed novel diagnostic systems for quantifying mitochondrial DNA heteroplasmy rate in urine using droplet digital PCR. In addition, we published our evidence on relation between genetic background including mitochondrial DNA heteroplasmy rate and prognosis in mitochondrial cardiomyopathy patients.
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Academic Significance and Societal Importance of the Research Achievements |
確立した診断法が存在しないミトコンドリア心筋症の診断率の向上は長年の課題であった。申請者らの開発した変異ミトコンドリアDNA定量化システムは、非侵襲的に入手可能な尿検体を用いてミトコンドリア心筋症の診断が可能となる手法であり、心筋生検という侵襲を必要としないという利点を有する。さらに現在定量化手法の存在しないミトコンドリアDNA欠失変異に対しても、欠失部位によらず定量化が可能である。本システムは臨床現場で活用できるミトコンドリア心筋症の診断ツールとしての有用性を持つ。さらに変異ミトコンドリアDNA率と心筋症重症度、予後との相関はミトコンドリア心筋症に対する心臓移植適応のエビデンス構築に役立つ。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Impact of measuring heteroplasmy of a pathogenic mitochondrial DNA variant at the single-cell level in individuals with mitochondrial disease2022
Author(s)
Imai-Okazaki A, Nitta KR, Yatsuka Y, Sugiura A, Arao M, Shimura M, Ebihara T, Onuki T, Ichimoto K, Ohtake A, Murayama K, Okazaki Y.
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Journal Title
J Inherit Metab Dis.
Volume: 45
Issue: 6
Pages: 1143-1150
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of Leigh syndrome with a high probability of cardiac manifestations in infantile-onset patients with m.14453G>A2022
Author(s)
Masaru Shimura, Takanori Onuki, Yohei Sugiyama, Tetsuro Matsuhashi, Tomohiro Ebihara, Takuya Fushimi, Makiko Tajika, Keiko Ichimoto, Ayako Matsunaga, Tomoko Tsuruoka, Kazuhiro R Nitta, Atsuko Imai-Okazaki, Yukiko Yatsuka, Yoshihito Kishita, Akira Ohtake, Yasushi Okazaki, Kei Murayama
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Journal Title
Mitochondrion.
Volume: 63
Pages: 1-8
Related Report
Peer Reviewed
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[Journal Article] Severe spinal cord hypoplasia due to a novel ATAD3A compound heterozygous deletion2022
Author(s)
Ebihara T, Nagatomo T, Sugiyama Y, Tsuruoka T, Osone Y, Shimura M, Tajika M, Ichimoto K, Naruke Y, Akiyama N, Lim SC, Yatsuka Y, Nitta KR, Kishita Y, Fushimi T, Okazaki A, Ohtake A, Okazaki Y, Murayama K.
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Journal Title
Mol Genet Metab Rep.
Volume: 33
Pages: 100912-100912
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of Leigh syndrome with a high probability of cardiac manifestations in infantile-onset patients with m.14453G?>?A2022
Author(s)
Shimura M, Onuki T, Sugiyama Y, Matsuhashi T, Ebihara T, Fushimi T, Tajika M, Ichimoto K, Matsunaga A, Tsuruoka T, Nitta KR, Imai-Okazaki A, Yatsuka Y, Kishita Y, Ohtake A, Okazaki Y, Murayama K.
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Journal Title
Mitochondrion
Volume: 63
Pages: 1-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Neonatal-onset mitochondrial disease: clinical features, molecular diagnosis and prognosis2021
Author(s)
Ebihara T, Nagatomo T, Sugiyama Y, Tsuruoka T, Osone Y, Shimura M, Tajika M, Matsuhashi T, Ichimoto K, Matsunaga A, Akiyama N, Ogawa-Tominaga M, Yatsuka Y, Nitta KR, Kishita Y, Fushimi T, Imai-Okazaki A, Ohtake A, Okazaki Y, Murayama K.
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Journal Title
Archives of Disease in Childhood - Fetal and Neonatal Edition
Volume: 107
Issue: 3
Pages: 329-334
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-term prognosis and genetic background of cardiomyopathy in 223 pediatric mitochondrial disease patients.2021
Author(s)
Imai-Okazaki A, Matsunaga A, Yatsuka Y, Nitta KR, Kishita Y, Sugiura A, Sugiyama Y, Fushimi T, Shimura M, Ichimoto K, Tajika M, Tominaga M, Ebihara T, Matsuhashi T, Tsuruoka T, Kohda M, Hirata T, Harashima H, Nojiri S, Takeda A, Nakaya A, Kogaki S, Sakata Y, Ohtake A, Murayama K, Okazaki Y.
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Journal Title
International Journal of Cardiology
Volume: 341
Pages: 48-55
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Validation and diagnosis of novel variants of mitochondrial diseases associated with the ECHS1 gene2022
Author(s)
Kishita Y, Sugiura A, Onuki T, Ebihara T, Matsuhashi T, Shimura M, Fushimi T, Ichino N, Nagatakidani Y, Nishihata H, Nitta KR, Yatsuka Y, Imai-Okazaki A, Yibo W, Osaka H, Ohtake A, Murayama K, Okazaki Y.
Organizer
第45回日本分子生物学会年会,
Related Report
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[Presentation] Neonatal-Onset Mitochondrial Disease: Clinical Features, Molecular Diagnosis, and Prognosi2022
Author(s)
Tomohiro Ebihara, Taro Nagatomo, Yohei Sugiyama, Tomoko Tsuruoka, Yoshiteru Osone, Masaru Shimura, Makiko Tajika, Tetsuro Matsuhashi, Keiko Ichimoto, Ayako Matsunaga, Nana Akiyama, Yukiko Yatsuka, Kazuhiro R. Nitta, Yoshihito Kishita, Takuya Fushimi, Atsuko Okazaki, Akira Ohtake, Yasushi Okazaki, Kei Murayama
Organizer
SSIEM Annual Symposium
Related Report
Int'l Joint Research
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[Presentation] Maternally inherited deafness, epilepsy and mental retardation is associated with m.12207G>A MT-TS2 mutation in a Japanese family2022
Author(s)
Sayaka Ajihara, Megumi Tsuruoka, Hiroko Harashima, Torayuki Okuyama, Yukiko Yatsuka, Atuko Okazaki, Yasushi Okazaki, Kei Murayama, Yuko Akioka, Akira Ohtake
Organizer
SSIEM Annual Symposium
Related Report
Int'l Joint Research
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