Analysis of the pathogenesis of cardiac Na channelopathies

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790720
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MAKIYAMA Takeru Kyoto University, 医学研究科, 助教 (30528302)
• Project Period (FY): 2009 – 2010
• Keywords: 不整脈 / 分子心臓病態学

Research Abstract

Mutations in SCN5A gene, encoding cardiac Na channels, are reported to cause a variety of arrhythmias. We performed genetic screening on sudden infant death syndrome (SIDS) and clarified that SCN5A mutations are prevalent in Japanese infants with life threatening arrhythmias, in addition, not only SCN5A gain-of-function type modulation (Long-QT syndrome type 3, but also loss-of-function (Brugada syndrome) may be a pathogenic basis of SIDS. Furthemore, we analysed TCAP gene, a member of Z-disk proteins which associate with the cardiac Na channels, on patients with inherited arrhythmias. The mutation might be associated with cardiac arrhythmias by modulating Na currents.

Research Products

• [Journal Article] A novel KCM2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil Syndrome. (2011)
  • Author(s): Doi T, Makiyama T, Morimoto T, Haruna Y, Tsuji K, Akao M, Takahashi Y, Kimura T, Horie M.
  • Journal Title: Circulation Cardiovascular Genetics.
  • URL: In press.
  • Peer Reviewed
• [Journal Article] Novel KCNE5 variants are associated with Brugada syndrome and idiopathic ventricular fibrillation. (2011)
  • Author(s): Ohno S, Zankov D, Ding W, Makiyama T, Doi T, Shizuta S, Itoh H, Nishio Y, Hattori T, Matsuura H, Horie M.
  • Journal Title: Circulation Arrhythmia and Electrophysiol.
  • URL: In press.
  • Peer Reviewed
• [Journal Article] Risk Determinants in Individuals With a Spontaneous Type 1 Brugada ECG. (2011)
  • Author(s): Miyamoto A, Hayashi H, Makiyama T, Yoshino T, Mizusawa Y, Sugimoto Y, Ito M, Xue JQ, Murakami Y, Horie M.
  • Journal Title: Circ J. 75(4) Pages: 1623-9
  • Peer Reviewed
• [Journal Article] Atrioventricular block-induced Torsades de Pointes with clinical and molecular backgrounds similar to congenital long QT syndrome. (2010)
  • Author(s): Oka Y, Itoh H, Ding WG, Shimizu W, Makiyama T, Ohno S, Nishio Y, Sakaguchi T, Miyamoto A, Kawamura M, Matsuura H, Horie M.
  • Journal Title: Circ J. 25;74(12) Pages: 2562-71
  • Peer Reviewed
• [Journal Article] Heart rate-dependent variability of cardiac events in type 2 congenital long-QT syndrome. (2010)
  • Author(s): Nagaoka I, Shimizu W, Mizusawa Y, Sakaguchi T, Itoh H, Ohno S, Makiyama T, Yamagata K, Makimoto H, Miyamoto Y, Kamakura S, Horie M.
  • Journal Title: Europace. 12(11)
  • Peer Reviewed
• [Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype : a Japanese multicenter study. (2010)
  • Author(s): Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, Makiyama T, Akao M, Ai T, Noda T, Miyazaki A, Miyamoto Y, Yamagishi M, Kamakura S, Horie M.
  • Journal Title: Heart Rhythm. 7(10) Pages: 1411-1418
  • Peer Reviewed
• [Journal Article] High prevalence of early repolarization in short QT syndrome. (2010)
  • Author(s): Watanabe H, Makiyama T, Koyama T, Kannankeril PJ, Seto S, Okamura K, Oda H, Itoh H, Okada M, Tanabe N, Yagihara N, Kamakura S, Horie M, Aizawa Y, Shimizu W.
  • Journal Title: Heart Rhythm. 7(5) Pages: 647-52
  • Peer Reviewed
• [Journal Article] 堀江稔家族性ベースメーカ植込み症例における遺伝的背景の検討-心臓Na+チャネル病 (2010)
  • Author(s): 牧山武, 静田聡, 赤尾昌治, 木村剛
  • Journal Title: Lamin A/C遺伝子関連心筋症-心電図 30 Pages: 201-209
  • Peer Reviewed
• [Journal Article] A novel SCN5A mutation associated with the linker between III and IV domains of Na (v) 1.5 in a neonate with fatal long QT syndrome. (2010)
  • Author(s): Yamamura K, Muneuchi J, Uike K, Ikeda K, Inoue H, Takahata Y, Shiokawa Y, Yoshikane Y, Makiyama T, Horie M, Hara T.
  • Journal Title: Int J Cardiol. 5;145(1) Pages: 61-64
  • Peer Reviewed
• [Journal Article] Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. (2009)
  • Author(s): Itoh H, Sakaguchi T, Ding WG, Watanabe E, Watanabe I, Nishio Y, Makiyama T, Ohno S, Akao M, Higashi Y, Zenda N, Kubota T, Mori C, Okajima K, Haruna T, Miyamoto A, Kawamura M, Ishida K, Nagaoka I, Oka Y, Nakazawa Y, Yao T, Jo H, Sugimoto Y, Ashihara T, Hayashi H, Ito M, Imoto K, Matsuura H, Horie M.
  • Journal Title: Circ Arrhythm Electrophysiol. 2(5) Pages: 511-523
  • Peer Reviewed
• [Journal Article] D85N, a KCNE1 polymorphism, is a disease-causing gene variant inlong QT syndrome. (2009)
  • Author(s): Nishio Y, Makiyama T, Itoh H, Sakaguchi T, Ohno S, Gong YZ, Yamamoto S, Ozawa T, Ding WG, Toyoda F, Kawamura M, Akao M, Matsuura H, Kimura T, Kita T, Horie M.
  • Journal Title: J Am Coll Cardiol. 25;54(9) Pages: 812-819
  • Peer Reviewed
• [Journal Article] Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome. (2009)
  • Author(s): Ohno S, Toyoda F, Zankov DP, Yoshida H, Makiyama T, Tsuji K, Honda T, Obayashi K, Ueyama H, Shimizu W, Miyamoto Y, Kamakura S, Matsuura H, Kita T, Horie M.
  • Journal Title: Hum Mutat. 30(4) Pages: 557-563
  • Peer Reviewed
• [Presentation] Both Gain-andLoss-of-Function Mutations in the Cardiac Na+ Channel Gene, SCN5A, are Associated with Sudden Infant Death Syndrome(SIDS). (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学学術集会(Focus session)
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] Dilated Cardiomyopathy : DCM, Case presentation. (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学会学術集会(Focussession)
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] Inherited VentricularArrhythmic Disorders in Asia : What's New and What's Different from US and Europe? (2010)
  • Author(s): 牧山武
  • Organizer: Heart Rhythm
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-05-15
• [Presentation] 学術諮問委員会指定トピックス【不整脈の遺伝子診断】:家族性ペースメーカー植込み症例における遺伝的背景の検討-心臓Na+チャネル病、lamin A/C関連心筋症- (2009)
  • Author(s): 牧山武
  • Organizer: 第24回日本不整脈学会学術大会/第26回日本心電学会学術集会合同学術集会
  • Place of Presentation: 京都
  • Year and Date: 20090702-20090704
• [Presentation] SCN5A and Lamin A/C genemutations are highly prevalent in patients with familial bradyarrhythmic disorders. (2009)
  • Author(s): 牧山武
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20090320-20090322