Gene identification of rare genetic diseases by Multi-Omics analysis
Project/Area Number |
19H03621
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | National Center for Global Health and Medicine (2020-2021) Yokohama City University (2019) |
Principal Investigator |
Miyake Noriko 国立研究開発法人国立国際医療研究センター, 研究所, 疾患ゲノム研究部 部長 (40523494)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 単一遺伝子疾患 / 網羅的ゲノム解析 / 発症病態解明 / 新規疾患遺伝子 / Multi-Omics / 全エクソーム解析 / 新規遺伝子候補 / オミックス解析 / 稀少難治性疾患 / 遺伝要因 / 遺伝子解析 / ゲノム解析 / MN1 / プロテオーム解析 / 相分離 / 遺伝学的解析 |
Outline of Research at the Start |
遺伝要因が未知のヒト稀少難治性疾患を対象に、網羅的遺伝子解析を行い、新規疾患遺伝子の同定を行う。更に、疾患病態解明を目的としてMulti-Omics解析を併用し、変異遺伝子が介する分子病理を解明し、診断法・予防法の開発と「治療戦略」構築を目指す。
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Outline of Final Research Achievements |
We performed comprehensive genetic analysis, mainly exome sequencing, to identity novel human disease genes. We collected samples together with detailed clinical information to understand the main phenotype, complications, and clinical course. The most impactful work is the identification of the MN1 gene for a new syndrome with craniofacial and brain abnormalities. Using Multi-Omics analysis, we revealed that this disease was caused by gain-of-function mechanism of MN1. In addtion, we reported the extremely rare cases caused by relatively newly identified disease genes, ABHD16A and COG1, in which only a few patients have been reported. By our review of the previoulsy reported cases and our cases, we reported the common clinical features which would be a great help for clinical diagnosis.
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Academic Significance and Societal Importance of the Research Achievements |
原因不明の稀少遺伝性難治疾患における原因究明は、患者・家族や医療者を含めた周囲の精神的・経済的負担の軽減の観点でも急務である。疾患原因遺伝子を同定することは、変異が来す分子病態・発症メカニズムを明らかにするための第一歩と位置づけられ、予防・治療法開発の契機となる。稀少遺伝性難治疾患の原因となりうるde novo 遺伝子変異は、一定の頻度で生じ、世界中どこでも発症しうる。本研究の成果は、日本に限定することなく、世界中の稀少遺伝子疾患の患者の診断や遺伝子カウンセリング、また医療側が適切な医療を行う上で非常に重要な情報を提供するものである。
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Report
(4 results)
Research Products
(77 results)
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[Journal Article] Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome2022
Author(s)
Miyatake S, Yoshida K, Koshimizu E, others, Miyake N, Shimohata T, Tanaka F, Mizuguchi T, Matsumoto N.
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Journal Title
Brain
Volume: 145
Issue: 3
Pages: 1139-1150
DOI
Related Report
Peer Reviewed
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[Journal Article] Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.2022
Author(s)
Hamanaka K, Miyake N, Mizuguchi T, Miyatake S, Uchiyama Y, Tsuchida N, Sekiguchi F, Mitsuhashi S, Tsurusaki Y, Nakashima M, Saitsu H, Yamada K, Sakamoto M, Fukuda H, Ohori S, Saida K, Itai T, Azuma Y, Koshimizu E, Fujita A, Erturk B, Hiraki Y, Ch'ng GS, Kato M, Okamoto N, Takata A, Matsumoto N.
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Journal Title
Genome Med
Volume: 14
Issue: 1
Pages: 40-40
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Recurrent de novo missense variants in GNB2 can cause syndromic intellectual disability2021
Author(s)
Tan NB, Pagnamenta AT, others, Matsumoto N, Miyake N, Sheffer R, Mor-Shaked H, Barnett CP, Byrne AB, Scott HS, Kraus A, Cappuccio G, Brunetti-Pierri N, Iorio R, Di Dato F, Pais LS, Yeung A, Tan TY, Taylor JC, Christodoulou J, White SM.
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Journal Title
Journal of Medical Genetics
Volume: 59
Issue: 5
Pages: 511-516
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A homozygous ABHD16A variant causes a complex hereditary spastic paraplegia with developmental delay, absent speech, and characteristic face2021
Author(s)
Miyake N, Silva S, Troncoso M, Okamoto N, Andachi Y, Kato M, Iwabuchi C, Hirose M, Fujita A, Uchiyama Y, Matsumoto N.
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Journal Title
Clinical Genetics
Volume: 101
Issue: 3
Pages: 359-363
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Valine metabolites analysis in ECHS1 deficiency2021
Author(s)
Kuwajima M, Kojima K, Osaka H, Hamada Y, Jimbo E, Watanabe M, Aoki S, Sato-Shirai I, Ichimoto K, Fushimi T, Murayama K, Ohtake A, Kohda M, Kishita Y, Yatsuka Y, Uchino S, Mimaki M, Miyake N, Matsumoto N, Okazaki Y, Ogata T, Yamagata T, Muramatsu K.
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Journal Title
Molecular Genetics and Metabolism Reports
Volume: 29
Pages: 100809-100809
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings2021
Author(s)
Ohashi K, Fukuhara S, Miyachi T, Asai T, Imaeda M, Goto M, Kurokawa Y, Anzai T, Tsurusaki Y, Miyake N, Matsumoto N, Yamagata T, Saitoh S
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Journal Title
J Autism Dev Disord
Volume: なし
Issue: 12
Pages: 4655-4662
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 22021
Author(s)
Faundes V, Goh S, Akilapa R, Bezuidenhout H, others, Miyake N, Benoit V, Lederer D, Banka S.
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Journal Title
Genetics in Medicine
Volume: 23
Issue: 7
Pages: 1202-1210
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Complete sequencing of expanded SAMD12 repeats by long-read sequencing with Cas9-mediated enrichment.2021
Author(s)
Mizuguchi T, Toyota T, Miyatake S, Mitsuhashi S, Doi H, Kudo Y, Kishida H, Hayashi N, Tusburaya RS, Kinoshita M, Fukuyama T, Fukuda H, Koshimizu E, Tsuchida N, Uchiyama Y, Fujita A, Takata A, Miyake N, Kato M, Tanaka F, Adachi H, Matsumoto N.
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Journal Title
Brain
Volume: 144
Issue: 4
Pages: 1103-1117
DOI
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Peer Reviewed / Open Access
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[Journal Article] Neuronal intranuclear inclusion disease presenting with an MELAS-like episode in chronic polyneuropathy2020
Author(s)
Ishihara T, Okamoto T, Saida K, Saitoh Y, Oda S, Sano T, Yoshida T, Morita Y, Fujita A, Fukuda H, Miyake N, Mizuguchi T, Saito Y, Sekijima Y, Matsumoto N and Takahashi Y
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Journal Title
Neurol Genet
Volume: 6
Issue: 6
DOI
Related Report
Peer Reviewed
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[Journal Article] Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia2020
Author(s)
Hiromoto Y, Azuma Y, Suzuki Y, Hoshina M, Uchiyama Y, Mitsuhashi S, Miyatake S, Mizuguchi T, Takata A, Miyake N, Kato M, Matsumoto N.
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Journal Title
Hum Genome Var
Volume: 7
Issue: 1
Pages: 43-43
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction2020
Author(s)
Sakamoto M, Kouhei D, Haniffa M, Silva S, Troncoso M, Santander P, Schonstedt V, Stecher X, Okamoto N, Hamanaka K, Mizuguchi T, Mitsuhashi S, Miyake N and Matsumoto N
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Journal Title
J Hum Genet
Volume: 65
Issue: 9
Pages: 751-757
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation2019
Author(s)
Guo L, Bertola DR, Takanohashi A, Saito A, Segawa Y, Yokota T, Ishibashi S, Nishida Y, Yamamoto GL, Franco JFdS, Honjo RS, Kim CA, Musso CM, Timmons M, Pizzino A, Taft RJ, (以下21名省略), Ikegawa S.
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Journal Title
The American Journal of Human Genetics
Volume: 104
Issue: 5
Pages: 925-935
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.2018
Author(s)
Otomo N, Takeda K, Kawai S, Kou I, Guo L, Osawa M, Alev C, Kawakami N, Miyake N, Matsumoto N, Yasuhiko Y, Kotani T, Suzuki T, Uno K, Sudo H, Inami S, Taneichi H, Shigematsu H, Watanabe K, Yonezawa I, Sugawara R, Taniguchi Y, Minami S, Kaneko K, Nakamura M, Matsumoto M, Toguchida J, Watanabe K, Ikegawa S.
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Journal Title
Journal of Medical Genetics
Volume: -
Issue: 9
Pages: 622-628
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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