Genetic background of inherited cardiac arrhythmias
Project/Area Number |
25461054
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular medicine
|
Research Institution | Kyoto University |
Principal Investigator |
Makiyama Takeru 京都大学, 医学(系)研究科(研究院), 助教 (30528302)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 臨床心臓学 / 不整脈 / イオンチャネル / 遺伝学 / iPS細胞 |
Outline of Final Research Achievements |
This study aimed to elucidate the phenotype-genotype relationship in the inherited arrhythmias and reveal the underlying mechanisms, especially, using a newly developed technology, ’patient specific induced pluripotent stem (iPS) cell model’. We identified a cardiac sodium channel mutation in a patient with sinus node dysfunction and epinephrine-induced QT prolongation. The electrophysiological properties of the mutant channels were closely associated with the overlapping clinical features of the patient. Regarding the disease-specific iPS model, we generated CPVT-iPS cell model and recapitulated arrhythmogenic features which were suppressed by a promising compound, S107. In addition, we established long QT syndrome-iPS model associated with an L-type Ca channel gene mutation and identified the impaired inactivation in the mutant channels. In LMNA-related cardiomyopathy, we investigated the impact of the type of mutation to the development of decreased left ventricular function.
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Cardiac sodium channel mutation associated with epinephrine-induced QT prolongation and sinus node dysfunction.2016
Author(s)
Chen J, Makiyama T, Wuriyanghai Y, Ohno S, Sasaki K, Hayano M, Harita T, Nishiuchi S, Yamamoto Y, Ueyama T, Shimizu A, Horie M, Kimura T.
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Journal Title
Heart Rhythm
Volume: 13(1)
Issue: 1
Pages: 289-298
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The genetics underlying acquired long QT syndrome: impact for genetic screening2015
Author(s)
Itoh H, Crotti L, Aiba T, Spazzolini C, Denjoy I, Fressart V, Hayashi K, Nakajima T, Ohno S, Makiyama T, Wu J, Hasegawa K, Mastantuono E, Dagradi F, Pedrazzini M, Yamagishi M, Berthet M, Murakami Y, Shimizu W, Guicheney P, Schwartz PJ, Horie M
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Journal Title
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Asymmetry of parental origin in Long QT syndrome. Preferential maternal transmission of KCNQ1 variants linked to channel dysfunction.2015
Author(s)
Itoh H, Berthet M, Fressart V, Denjoy I, Maugenre S, Klug D, Mizusawa Y, Makiyama T, Hofman N, Shimizu W, Wilde AAM, Schulze-Bahr E, Horie M, Tezenas du Montcel S, Guicheney P.
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Journal Title
European Journal of Human Genetics
Volume: -
Issue: 8
Pages: 1160-6
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome2015
Author(s)
Kamakura T, Wada M, Nakajima I, Ishibashi K, Miyamoto K, Okamura H, Noda T, Aiba T, Takaki H, Yasuda S, Ogawa H, Shimizu W, Makiyama T, Kimura T, Kamakura S, Kusano K
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Gain-of-function KCNH2 mutations in patients with Brugada syndrome.2014
Author(s)
Wang Q, Ohno S, Ding WG, Fukuyama M, Miyamoto A, Itoh H, Makiyama T, Wu J, Bai J, Hasegawa K, Shinohara T, Takahashi N, Shimizu A, Matsuura H, Horie M.
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Journal Title
J Cardiovasc Electrophysiol.
Volume: 25
Issue: 5
Pages: 522533-522533
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Long QT Syndrome Type8: Novel CACNA1C Mutations Causing QT Prolongation and Variant Phenotypes.2014
Author(s)
Fukuyama M, Wang Q, Kato K, Ohno S, Ding WG, Toyoda F, Itoh H, Kimura H, Makiyama T, Ito M, Matsuura H, Horie M.
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Journal Title
Europace.
Volume: in press
Issue: 12
Pages: 1828-37
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel HCN4 mutation, G1097W, is associated with atrioventricular block2014
Author(s)
Zhou J, Ding WG, Makiyama T, Miyamoto A, Matsumoto Y, Kimura H, Tarutani Y, Zhao J, Wu J, Zang WJ, Matsuura H, Horie M
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Journal Title
Circ J
Volume: 78
Pages: 938-942
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.2014
Author(s)
Abe K, Machida T, Sumitomo N, Yamamoto H, Ohkubo K, Watanabe I, Makiyama T, Fukae S, Kohno M, Harrell DT, Ishikawa T, Tsuji Y, Nogami A, Watabe T, Oginosawa Y, Abe H, Maemura K, Motomura H, Makita N.
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Journal Title
Circ Arrhythm Electrophysiol
Volume: in press
Issue: 3
Pages: 511-517
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Brugada syndrome in spinal and bulbar muscular atrophy.2014
Author(s)
Araki A, Katsuno M, Suzuki K, Banno H, Suga N, Hashizume A, Mano T, Hijikata Y, Nakatsuji H, Watanabe H, Yamamoto M, Makiyama T, Ohno S, Fukuyama M, Morimoto S, Horie M, Sobue G
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Journal Title
Neurology
Volume: 82
Issue: 20
Pages: 1813-1821
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench.2014
Author(s)
Kato K, Makiyama T, Wu J, Ding WG, Kimura H, Naiki N, Ohno S, Itoh H, Nakanishi T, Matsuura H, Horie M.
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Journal Title
J Cardiovasc Electrophysiol
Volume: 25
Issue: 1
Pages: 66-73
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels.2014
Author(s)
Hasegawa K, Ohno S, Ashihara T, Itoh H, Ding WG, Toyoda F, Makiyama T, Aoki H, Nakamura Y, Delisle BP, Matsuura H, Horie M.
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Journal Title
Heart Rhythm
Volume: 11
Issue: 1
Pages: 67-75
DOI
Related Report
Peer Reviewed
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[Journal Article] Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture2013
Author(s)
Kamakura T, Makiyama T, Sasaki K, Yoshida Y, Wuriyanghai Y, Chen J, Hattori T, Ohno S, Kita T, Horie M, Yamanaka S, Kimura T.
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Journal Title
Circ J
Volume: 77
Pages: 1307-14
NAID
Related Report
Peer Reviewed
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[Journal Article] A novel SCN5A mutation demonstrating a variety of clinical phenotypes in familial sick sinus syndrome2013
Author(s)
Nakajima S, Makiyama T, Hanazawa K, Kaitani K, Amano M, Hayama Y, Onishi N, Tamaki Y, Miyake M, Tamura T, Kondo H, Motooka M, Izumi C, Nakagawa Y, Horie M
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Journal Title
Intern Med
Volume: 52
Pages: 1805-8
NAID
Related Report
Peer Reviewed
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[Journal Article] Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan2013
Author(s)
Kawamura M, Ohno S, Naiki N, Nagaoka I, Dochi K, Wang Q, Hasegawa K, Kimura H, Miyamoto A, Mizusawa Y, Itoh H, Makiyama T, Sumitomo N, Ushinohama H, Oyama K, Murakoshi N, Aonuma K, Horigome H, Honda T, Yoshinaga M, Ito M, Horie M
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Journal Title
Circ J
Volume: 77
Pages: 1705-13
NAID
Related Report
Peer Reviewed
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[Journal Article] Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.52013
Author(s)
Ishikawa T, Takahashi N, Ohno S, Sakurada H, Nakamura K, On YK, Park JE, Makiyama T, Horie M, Arimura T, Makita N, Kimura A
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Journal Title
Circ J
Volume: 77
Pages: 959-67
Related Report
Peer Reviewed
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