Novel molecular basis of cardriac conduction disturbance associated with a collagene gene mutation

• Project/Area Number: 15K15311
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Nagasaki University
• Principal Investigator: MAKITA Naomasa 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00312356)
• Co-Investigator(Kenkyū-buntansha): 牧山 武 京都大学, 医学研究科, 助教 (30528302)
• Co-Investigator(Renkei-kenkyūsha): ARAI Yuji 独立行政法人国立循環器病研究センター, 研究所, 室長 (30202724) ; ISHIKAWA Taisuke 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60708692)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: コラーゲン / 進行性心臓伝導障害 / ノックインマウス / CRISPR/Cas9 / 心臓伝導障害 / CRISPR/cas9 / CRISPR/CAS

Outline of Final Research Achievements

We found a mutation in type 6 collagen (COL6A2) in several families with progressive cardiac conduction defect. COL6A2 was evenly expressed in mouse ventricular wall during the embryonic stage, which became more restricted at the endocardial wall, age-dependently. At the age of one month, COL6A2 was observed nearly exclusively at the cardiac conduction system. Contrary to our expectation, COL6A2 mutation knock-in mice established by using CRISPR/Cas9 system showed no ECG abnormalities even 12 months after birth.

Research Products

• [Int'l Joint Research] INSERM/CNRS(フランス)
• [Int'l Joint Research] INSERM(フランス)
• [Int'l Joint Research] INSERM/CNRS(フランス)
• [Journal Article] Lack of genotype-phenotype correlation in Brugada syndrome and sudden arrhythmic death syndrome families with reported pathogenic SCN1B variants. (2018)
  • Author(s): Gray B, Hasdem C, Ingles J, Aiba T, Makita N, Probst V, Wilde A, Newbury-Ecob R, Sheppard M, Semsarian C, Sy R, Behr E
  • Journal Title: Heart Rhythm Volume: in Press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node (2018)
  • Author(s): Kozasa Yuko、Nakashima Noriyuki、Ito Masayuki、Ishikawa Taisuke、Kimoto Hiroki、Ushijima Kazuo、Makita Naomasa、Takano Makoto
  • Journal Title: J Physiol Volume: 596 Pages: 809-825
  • DOI: 10.1113/jp275303
  • Peer Reviewed / Open Access
• [Journal Article] The Phenotypic Spectrum of a Mutation?Hotspot Responsible for the?Short QT Syndrome (2017)
  • Author(s): Hu D, Li Y, Zhang J, Pfeiffer R, Gollob MH, Healey J, Harrell DT, Makita N, Abe H, Sun Y, Guo J, Zhang L, Yan G, Mah D, Walsh EP, Leopold HB, Giustetto C, Gaita F, Zienciuk-Krajka A, Mazzanti A, Priori SG, Antzelevitch C, Barajas-Martinez H
  • Journal Title: JACC: Clinical Electrophysiology Volume: 3 Pages: 727-743
  • DOI: 10.1016/j.jacep.2016.11.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Letter to the Editor (2017)
  • Author(s): Ishikawa T, Makita N, Aoki H, Saida Y
  • Journal Title: J Vet Intern Med Volume: 31 Pages: 967-968
  • DOI: 10.1111/jvim.14781
  • Peer Reviewed / Open Access
• [Journal Article] Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction (2017)
  • Author(s): Ishikawa T, Horie M, et al.
  • Journal Title: Heart rhythm Volume: 印刷中 Pages: 717-724
  • DOI: 10.1016/j.hrthm.2017.01.020
  • Peer Reviewed / Open Access
• [Journal Article] Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes (2017)
  • Author(s): Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, ・・・Horie M, Kamiya K, Fukuda K.
  • Journal Title: Biochemistry and biophysics reports Volume: 9 Pages: 245-256
  • DOI: 10.1016/j.bbrep.2017.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Gene-Based Risk Stratification for Cardiac Disorders in <i>LMNA</i> Mutation Carriers. (2017)
  • Author(s): Nishiuchi S, Makiyama T, Aiba T, Nakajima K, Hirose S, Kohjitani H, Yamamoto Y, Harita T, Hayano M, Wuriyanghai Y, Chen J, Sasaki K, Yagihara N, Ishikawa T, Onoue K, Murakoshi N, Watanabe I, Ohkubo K, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, et.al
  • Journal Title: Circulation Cardiovascular Genetics Volume: 6
  • DOI: 10.1161/circgenetics.116.001603
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Postmortem genetic analysis of sudden unexpected death in infancy: neonatal genetic screening may enable the prevention of sudden infant death (2017)
  • Author(s): Oshima Y, Yamamoto T, Ishikawa T, Mishima H, Matsusue A, Umehara T, Murase T, Abe Y, Kubo SI, Yoshiura KI, Makita N, Ikematsu K.
  • Journal Title: Journal of Human Genetics Volume: 62 Pages: 989-995
  • DOI: 10.1038/jhg.2017.79
  • Peer Reviewed
• [Journal Article] Progressive atrial conduction system defects associated with bone malformation caused by a connexin45 mutation (2017)
  • Author(s): Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau AE, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin JP, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura KI, Redon R, Schott JJ, Makita N.
  • Journal Title: J Am Coll Cardiol Volume: 70 Pages: 358-370
  • DOI: 10.1016/j.jacc.2017.05.039
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genotype-Phenotype Correlation of <i>SCN5A</i> Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. (2017)
  • Author(s): Yamagata K, Horie M, et al.
  • Journal Title: Send to Circulation. Volume: 印刷中 Pages: 0-0
  • DOI: 10.1161/circulationaha.117.027983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation. (2017)
  • Author(s): Yamamoto Y, Makiyama T*, Harita T, Sasaki K, Wuriyanghai Y, Hayano M, Nishiuchi S, Kohjitani H, Hirose S, Chen J, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Motomura H, Yoshida Y, Horie M, Makita N, Kimura T
  • Journal Title: Human Molecular Genetics Volume: - Pages: 1670-1677
  • DOI: 10.1093/hmg/ddx073
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel de novo calmodulin mutation in a 6-year-old boy who experienced an aborted cardiac arrest (2017)
  • Author(s): Takahashi K, Ishikawa T, Makita N, Takefuta K, Nabeshima T, Nakayashiro M
  • Journal Title: HeartRhythm Case Reports Volume: 3 Pages: 69-72
  • DOI: 10.1016/j.hrcr.2016.09.004
  • Peer Reviewed / Open Access
• [Journal Article] Progressive atrial conduction system defects associated with bone malformation caused by a connexin45 mutation (2017)
  • Author(s): Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau A, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin JP, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura KI, Redon R, Schott JJ, Makita N.
  • Journal Title: J Am Coll Cardiol Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Embryonic type Na+ channel beta-subunit, SCN3B masks the disease phenotype of Brugada syndrome (2016)
  • Author(s): Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
  • Journal Title: Scientific Reports Volume: 311 Pages: 34198-34198
  • DOI: 10.1038/srep34198
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I (2016)
  • Author(s): Daumy X, Amarouch MY, Lindenbaum P, Charpentier E, Bianchi B, Nafzger S, Baron E, Fouchard S, Thollet A, Kyndt F, Barc J, Le Scouarnec S, Makita N, Le Marec H, Dina C, Gourraud JB, Probst V, Abriel H, Redon R, Schott JJ
  • Journal Title: Int J Cardiol Volume: 207 Pages: 349-358
  • DOI: 10.1016/j.ijcard.2016.01.052
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inherited bradyarrhythmia: A diverse genetic background (2016)
  • Author(s): Ishikawa T, Tsuji Y, Makita N
  • Journal Title: J Arrhythm Volume: 印刷中 Pages: 352-358
  • DOI: 10.1016/j.joa.2015.09.009
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Variants in the SCN5A Promoter Associated With Various Arrhythmia Phenotypes (2016)
  • Author(s): Yagihara N,Minamino T,33名中28番
  • Journal Title: Journal of American Heart Association Volume: 19 Pages: 644-650
  • DOI: 10.1161/jaha.116.003644
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Reply: Search for Evidence-Based Medicine for Brugada Syndrome: The Complex Network of the Brugada Syndrome (2016)
  • Author(s): Nademanee K, Raju H, De Noronha S, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal A. C. Christiansen M, Tan H. L, Wilde A. A, Nogami A, Sheppard M. N, Veerakul G, Behr E. R.
  • Journal Title: J Am Coll Cardiol Volume: 67 Pages: 1658-1659
  • DOI: 10.1016/j.jacc.2016.01.032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel mutation in the alpha-myosin heavy chain gene is associated with sick sinus syndrome (2016)
  • Author(s): Ishikawa T, Jou CJ, Nogami A, Kowase S, Arrington CB, Barnett SM, Harrell DT, Arimura T, Tsuji Y, Kimura A, Makita N
  • Journal Title: Circulation Arrhythmia and Electrophysiology Volume: 8 Pages: 400-108
  • DOI: 10.1161/circep.114.002534
  • NAID: 120005672451
  • Peer Reviewed / Acknowledgement Compliant
• [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.
  • Journal Title: Heart Rhythm Volume: 13(1) Pages: 289-298
  • DOI: 10.1016/j.hrthm.2015.08.021
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Genetics Underlying Acquired Long QT Syndrome. Impact on genetic screening. (2016)
  • 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.
  • Journal Title: Eur Heart J. Volume: 37 (18) Pages: 1456-1464
  • DOI: 10.1093/eurheartj/ehv695
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction. (2016)
  • 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.
  • Journal Title: Eur J Hum Genet Volume: - Pages: 1160-1166
  • DOI: 10.1038/ejhg.2015.257
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] LMNA cardiomyopathy detected in Japanese arrhythmogenic right ventricular cardiomyopathy cohort (2016)
  • Author(s): Kato K, Takahashi N, Fujii Y, Umehara A, Nishiuchi S, Makiyama T, Ohno S, Horie M
  • Journal Title: Journal of Japanese College of Cardiology. Volume: 印刷中 Pages: 346-51
  • DOI: 10.1016/j.jjcc.2015.10.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel SCN10A variants associated with Brugada syndrome (2016)
  • Author(s): Fukuyama M, Ohno S, Makiyama T, Horie M
  • Journal Title: Europace. Volume: 印刷中
  • DOI: 10.1093/cvr/cvv042
  • Peer Reviewed
• [Journal Article] Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome (2015)
  • Author(s): Harrell DT, Ashihara T, Ishikawa T, et al.
  • Journal Title: Int J Cardio Volume: 190 Pages: 1095-1104
  • DOI: 10.1016/j.ijcard.2015.04.090
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation (2015)
  • Author(s): Hayashi K, Konno T, Tada H, Tani S, Liu L, Fujino N, Nohara A, Hodatsu A, Tsuda T, Tanaka Y, Kawashiri MA, Ino H, Makita N, Yamagishi M.
  • Journal Title: Circ Arrhythm Electrophysiol Volume: 8 Pages: 1095-104
  • DOI: 10.1161/circep.114.002519
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Mechanisms Underlying Urate-Induced Enhancement of Kv1.5 Channel Expression in HL-1 Atrial Myocytes (2015)
  • Author(s): Maharani N, Ting YK, Cheng J, Hasegawa A, Kurata Y, Li P, Nakayama Y, Ninomiya H, Ikeda N, Morikawa K, Yamamoto K, Makita N, Yamashita T, Shirayoshi Y, Hisatome I.
  • Journal Title: Circ J Volume: 79 Issue: 12 Pages: 2659-2668
  • DOI: 10.1253/circj.CJ-15-0416
  • NAID: 130005110934
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome (2015)
  • Author(s): Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal AC, Christiansen M, Tan HL, Wilde AA, Nogami A, Sheppard MN, Veerakul G, Behr ER
  • Journal Title: J Am Coll Cardiol Volume: 66(18) Pages: 1976-1986
  • DOI: 10.1016/j.jacc.2015.08.862
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Genetic and Biophysical Basis of Calmodulinopathy, and Functional Rescue by Genome-Editing in Patient-Derived iPS Cardiomyocytes (2017)
  • Author(s): Makita N.
  • Organizer: 20th International Symposium on Calcium Binding Proteins and Calcium Function in Health and Disease
  • Int'l Joint Research / Invited
• [Presentation] Genetic Mutation of Brugada Syndrome (2017)
  • Author(s): Makita N.
  • Organizer: Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research / Invited
• [Presentation] Brugada Syndrome: Basic and Clinical Updates, Advancement of Basic Research (2017)
  • Author(s): Makita N.
  • Organizer: 13th Annual Congress European Cardiac Arrhythmia Society
  • Int'l Joint Research / Invited
• [Presentation] Multinational genome-wide association study in long QT syndrome identifies a role for common genetic variation in disease susceptibility and points to a polygenic architecture in mutation-negative cases (2017)
  • Author(s): Lahrouchi N, Makita N et al.
  • Organizer: Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research
• [Presentation] De novo and Familial Connexin45 Mutant R75H Causes Progressive Atrioventricular Block Associated with Craniofacial and Dentodigital Dysmorphisms (2017)
  • Author(s): Makita N, Seki A, Ishikawa T, Dawmy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau A, Aurelie T, Swanny F, Stephanie B, Parent P, Shibata Y, Perrin JJ, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura K, Redon R, Schott J, J.
  • Organizer: Printemps de la Cardiologie Recherche Fondamentale et Clinique
  • Int'l Joint Research / Invited
• [Presentation] Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers (2017)
  • Author(s): Nishiuchi S, Makiyama T, Aiba T, Nakajima K, Ishikawa T, Murakoshi N, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, Saito Y, Oginosawa Y, Nogami A, Aonuma K, Kusano K, Makita N, Shimizu W, Horie M, Kimura T.
  • Organizer: The 10th Asia Pacific Heart Rhythm Sosiety Scientific Session
  • Int'l Joint Research
• [Presentation] CALM2-D134H Mutation Associated with Long-QT Syndrome Prevents Inactivation of L-type Ca2+ Currents in Human iPS Cell Derived Cardiomyocytes. (2017)
  • Author(s): Yamamoto Y, Makiyama T, Harita T, Hayano M, Nishiuchi S, Wuriyanghai Y, Kohjitani H, Hirose S, Yokoi F, Ishikawa T, Ohno S, Chinabayashi K, Suda K, Yoshida Y, Horie M, Makita N, Kimura T.
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research
• [Presentation] Sick sinus syndrome caused by HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular non-compaction (2017)
  • Author(s): Ishikawa T, Ohno S, Murakami T, Yoshida K, Fukuoka T, Mishima H, Kimoto H, Aiba T, Nogami A, Sumitomo N, Shimizu W, Horigome H, Yoshiura KI, Horie M, Makita N.
  • Organizer: Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research
• [Presentation] Mutation in L-type Calcium Channel Cav1.3 (CACNA1D) Underlying a Consanguineous Family Associated with Congenital AV Block and Deaf-Blindness (2017)
  • Author(s): Kimoto H, Ishikawa T, Mishima H, Hasdemir C, Yoshiura K, Makita N.
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research
• [Presentation] Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers in Japan (2017)
  • Author(s): Nishiuchi S, Aiba T, Makiyama T, Nakajima K, Yagihara N, Ishikawa T, Onoue K, Murakoshi N, Watanabe I, Ohkubo K, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, Saito Y, Oginosawa Y, Nogami A, Aonuma K, Kusano K, Makita N, Shimizu W, Horie M, Kimura T.
  • Organizer: American Heart Association Annual Scientific Session 2017
  • Int'l Joint Research
• [Presentation] CALM2-D134H Mutation Associated With Long-QT Syndrome Delayed Inactivation of L-type Ca2+ Currents in Human iPS Cells Derived Cardiomyocytes. (2017)
  • Author(s): Yamamoto Y, Makiyama T, Harita T, Hayano M, Nishiuchi S, Wuriyanghai Y, Kohjitani H, Hirose S, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Suda K, Yoshida Y, Horie M, Makita N, Kimura T.
  • Organizer: American Heart Association Annual Scientific Session 2017
  • Int'l Joint Research
• [Presentation] lL-cis-Diltiazem Ameliorates Impaired Calcium Channel Inactivation in a Patient-Specific Stem Cell Model of Long-QT Syndrome with a Calmodulin Mutation (2017)
  • Author(s): Yokoi F, Makiyama T, Harita T, Yamamoto Y, Hayano M, Nishiuchi S, Kohjitani H, Wuriyanghai Y, Hirose S, Toyoda F, Yoshida Y, Makita N, Horie M, Kimura T.
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session
• [Presentation] Genetics of Familial Atrial Fibrillation (2017)
  • Author(s): Ishikawa T, Makita N.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] Genetic-based risk stratification for cardiac disorders in LMNA mutation carriers (2017)
  • Author(s): Nishiuchi S, Aiba T, Nakajima K, Hirose S, Kohjitani H, Yamamoto Y, Harita T, Hayano M, Sasaki K, Ishikawa T, Onoue K, Saito Y, Kusano K, Makita N, Shimizu W, Horie M, Kimura T.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] Genotype-Phenotype Correlation of SCN5A Mutations for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome: A Japanese Multicenter Registry (2017)
  • Author(s): Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Fukushima-Kusano K, Kamakura S, Yasuda S, Ogawa H, Y. M, Kapplinger J, Ackerman M, Shimizu W.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation (2017)
  • Author(s): Yamamoto Y, Makiyama T, Harita T, Sasaki K, Wuriyanghai Y, Nishiuchi S, Kohjitani H, Hirose S, Ishikawa T, Motomura H, Ohno S, Yoshida Y, Horie M, Makita N, Kimura T.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] Calmodulin Mutations Responsible for Long QT Syndrome and Functional Rescue using a CRISPR/Cas9 System (2017)
  • Author(s): 蒔田直昌.
  • Organizer: 第94回日本生理学会大会
  • Invited
• [Presentation] ブルガダ症候群の予後予測を目指す変異心筋Naチャネルの機能解析 (2017)
  • Author(s): 下河舞子, 木本浩貴, 石川泰輔, 蒔田直昌.
  • Organizer: 第68回西日本生理学会
• [Presentation] Mutation Spot-sensitive Clinical Features and Risk of Life-threatening Arrhythmia in Long QT Syndrome Type 1 in Japan (2017)
  • Author(s): Aiba T, Makimoto H, Yagihara N, Watanabe H, Ohno S, Hayashi K, Sumitomo N, Yoshinaga M, Morita H, Miyamoto Y, Makita N, Horie M, Yasuda S, Kusano K, Shimizu W.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] Mutations in Desmin Gene Uncover Phenotypic Overlap between Progressive Cardiac Conduction Defect with Muscular Dystrophy and Cardiomyopathy (2017)
  • Author(s): 木本浩貴, 石川泰輔, 町田紘子, 森田宏, 住友直方, 中村一文, 伊藤浩, バーク・ジュリアン, ショット・ジョンジャック, 蒔田直昌.
  • Organizer: 第81回日本循環器学会学術集会
• [Presentation] De novo and Familial Connexin45 Mutant R75H Causes Progressive Atrioventricular Block Associated with Craniofacial and Dentodigital Dysmorphisms (2017)
  • Author(s): Makita N, Seki A, Ishikawa T, Schott JJ. et al.
  • Organizer: Printemps de la Cardiologie Recherche Fondamentale et Clinique
  • Place of Presentation: La Cite des Congres, Nantes, France
  • Invited
• [Presentation] Calmodulin Mutations Responsible for Long QT Syndrome and Functional Rescue using a CRISPR/Cas9 System (2017)
  • Author(s): Makita N.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Invited
• [Presentation] Mutations in Desmin Gene Uncover Phenotypic Overlap between Progressive Cardiac Conduction Defect with Muscular Dystrophy and Cardiomyopathy (2017)
  • Author(s): 木本浩樹, 町田紘子, 森田宏, 住友直方, 中村一文, 伊藤浩, バーク・ジュリアン, ショット・ジョンジャック, 蒔田直昌.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂音楽堂（石川県金沢市）
• [Presentation] Sick sinus syndrome caused by HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular non-compaction (2017)
  • Author(s): Ishikawa T, Ohno S, Murakami T, Yoshida K, Fukuoka T, Mishima H, Kimoto H, Aiba T, Nogami A, Sumitomo N, Shimizu W, Horigome H, Yoshiura K. I, Horie M, Makita N.
  • Organizer: Heart Rhythm Society Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Int'l Joint Research
• [Presentation] Multinational genome-wide association study in long QT syndrome identifies a role for common genetic variation in disease susceptibility and points to a polygenic architecture in mutation-negative cases (2017)
  • Author(s): Lahrouchi N, Tadros R, Makita N. et al
  • Organizer: Heart Rhythm Society Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Int'l Joint Research
• [Presentation] International Calmodulinopathy Registry (ICaMR) (2016)
  • Author(s): Crotti L, Makita N.
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: New Orleands, USA
• [Presentation] Selective therapeutic targeting of ion channel rare variants predisposing to lone atrial fibrillation (2016)
  • Author(s): Hayashi K, Fujino N, Tsuda T, Tanaka Y, Ino H, Makita N, Yamagishi M.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Broader Genetic Spectrum of Familial Atrial Arrhythmias Involving Rare Variations in the Common Arrhythmia-Susceptible Genes (2016)
  • Author(s): Ishikawa T, Mishima H, Ohno S, Harrell DT, Tsuji Y, Yoshiura K, Horie M, Makita N.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Overview of Genes Related to Cardiac Conduction (2016)
  • Author(s): Makita N.
  • Organizer: Korean Heart Rhythm Society 8th Annual Scientific Session
  • Place of Presentation: KINTEX,Korea
  • Int'l Joint Research / Invited
• [Presentation] Common genetic variants at SCN5A, SCN10A, and HEY2 are associated with cardiac conduction disturbance in patients with Brugada syndrome (2016)
  • Author(s): Murakoshi N, Xu D, Nogami A, Makita N, Sekiguchi Y, Kurosaki K, Kowase S, Naruse Y, Aonuma K.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Catheter Ablation of Brugada Syndrome：Further Evidence of Conduction Delay in the Right Ventricular Subepicardium as Mechanism of Brugada ECG and Ventricular Fibrillation (2016)
  • Author(s): Nakagawa H, Sakamoto Y, Yamashiro K, Takagi M, Kusano K, Noda T, Yamazaki M, Honjo H, Makita N, Tsuchiya T, Hoogeudiik MG, Nademanee K.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Novel de novo Calmodulin Mutation in a Pre-school boy Experiencing Aborted Cardiac Arrest (2016)
  • Author(s): Takahashi K, Makita N.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] Modeling of long-QT syndrome associated with a calmodulin mutation using human induced pluripotent stem cells (2016)
  • Author(s): Yamamoto Y, Makiyama T, Harita T, Sasaki K, Hayano M, Nishiuchi S, Wuriyanghai Y, Kohjitani H, Hirose S, Cheng J, Ishikawa T, Ohno S, Yoshida Y, Horie M, Makita N, Kimura T.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
• [Presentation] ECG Screening of 1-month-old Infants May Prevent Out-of-hospital Cardiac Arrest in Infancy (2016)
  • Author(s): Yoshinaga M, Ohno S, Ushinohama H, Sato S, Miyamoto T, Tauchi N, Horigome H, Sumitomo N, Shiraishi H, Ichida F, Hata T, Nomura Y, Horie M, Makita N, Nagashima M.
  • Organizer: American Heat Association Scientific Meeting 2016
  • Place of Presentation: New Orleans Convention Center, USA
• [Presentation] 歯牙骨格形成異常を合併する洞不全症候群に固定されたコネキシン45遺伝子変異と機能異常. (2016)
  • Author(s): 木本浩樹, 石川泰輔, 西井明子, 斎藤加代子, 三嶋博之, 大槻早紀, 辻幸臣, 吉浦孝一郎, 萩原誠久, 蒔田直昌.
  • Organizer: 第67回西日本生理学会
  • Place of Presentation: レインボー桜島（鹿児島県鹿児島市）
• [Presentation] Electrophysiological Features of Patient-specific Human-induced Pluripotent Stem Cell-derived Cardiomyocytes Carrying the SCN5A-D1275N Mutation (2016)
  • Author(s): 早野 護、牧山 武
  • Organizer: 日本循環器学会
  • Place of Presentation: 仙台、仙台国際会議場
  • Year and Date: 2016-03-18
• [Presentation] SCN5A and ventricular arrhythmias. (2015)
  • Author(s): Makita N
  • Organizer: Asian Pacific Heart Rhythm Society
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2015-11-22
  • Int'l Joint Research / Invited
• [Presentation] Cardiac Sodium Channel Mutation Associated With Epinephrine-Induced QT Prolongation and Sinus Node Dysfunction, (2015)
  • Author(s): 陳 嘉容、牧山 武
  • Organizer: 日本不整脈学会／日本心電学会
  • Place of Presentation: 京都、京都国際会議場
  • Year and Date: 2015-07-28
• [Presentation] New genes for Progressive Cardiac Conduction Disease (2015)
  • Author(s): Makita N
  • Organizer: Heart Rhythm Society
  • Place of Presentation: Boston,USA.
  • Year and Date: 2015-05-14
  • Int'l Joint Research / Invited
• [Presentation] Structural and Electrophysiological Characteristic of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes, (2015)
  • Author(s): 牧山 武
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] Genetic Backgrounds of Patients with Clinically Diagnosed Idiopathic Ventricular Fibrillation (2015)
  • Author(s): 糀谷 泰彦、牧山 武
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2015-04-24
• [Book] 不整脈診療クリニカルクエスチョン200 (2015)
  • Author(s): 蒔田直昌
  • Total Pages: 333
  • Publisher: 診断と治療社
• [Book] 不整脈症候群 (2015)
  • Author(s): 蒔田直昌
  • Total Pages: 196
  • Publisher: 南江堂