Elucidation of pathogenesis and clinical characteristics, establishment of the therapy in patients with LQTS caused by calcium related gene variants

• Project/Area Number: 18K07875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Ohno Seiko 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (20610025)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 先天性QT延長症候群 / カルシウムチャネル / カルモジュリン / CACNA1C / CALM1 / CALM2 / CACNA1c / Calmodulin / RYR2 / LQTS / LQT8 / LQT15 / カルシウムイオンチャネル / リアノジン

Outline of Final Research Achievements

Congenital long QT syndrome (LQTS) is mainly caused by mutations in genes encoding potassium and sodium channels. Along with the advances in the genetic analysis, LQTS caused by mutations in genes encoding other types of ion channels have been frequently reported. Therefore, we performed analysis targeting for the genes encoding calcium related ion channels and proteins.
Mutations in CACNA1C encoding L-type calcium channel are the cause for LQTS type 8, and the prevalence of it among LQTS patients has proved to be higher than it reported. Now we are conducting the functional analysis of the mutant L-type calcium channel. CALM1-3 encode calmodulin which works for the binding between calcium ion and proteins. We identified several mutations in CALM1-3 in LQTS patients. Their mutations are all de novo, and the phenotypes of them were very severe. RYR2 is a gene encoding cardiac ryanodine channel (RyR2), and we elucidated that loss-of-function type RyR2 caused LQTS.

Academic Significance and Societal Importance of the Research Achievements

先天性QT延長症候群（LQTS）は突然死を来す遺伝性疾患である。原因遺伝子は報告されているものの、変異が同定されない場合があり、カルシウムイオン（Ca2+）関連遺伝子の変異が考えられた。そこで次世代シークエンサーを用いてLQTS患者の遺伝子を解析したところ、カルシウムチャネルをコードするCACNA1C、様々なタンパクとCa2+との結合に関わるカルモジュリンをコードする遺伝子、および細胞内Ca2+をコントロールするリアノジンチャネルをコードするRYR2に変異を同定した。これらの遺伝子変異の解析を実施することによって、これまで報告の少ないCa2+関連のLQTSについて明らかにすることができた。

Research Products

• [Int'l Joint Research] University of Milano-Bicocca(イタリア)
• [Int'l Joint Research] Amsterdam University(オランダ)
• [Journal Article] Impact of the T-wave characteristics on distinguishing arrhythmogenic right ventricular cardiomyopathy from healthy children (2021)
  • Author(s): Imamura Tomohiko、Sumitomo Naokata、Muraji Shota、Yasuda Kazushi、Nishihara Eiki、Iwamoto Mari、Tateno Shigeru、Doi Shozaburo、Hata Tadayoshi、Kogaki Shigetoyo、Horigome Hitoshi、Ohno Seiko、Ichida Fukiko、Nagashima Masami、Makiyama Takeru、Yoshinaga Masao
  • Journal Title: International Journal of Cardiology Volume: 323 Pages: 168-174
  • DOI: 10.1016/j.ijcard.2020.08.088
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer. (2021)
  • Author(s): Hasegawa K, Ito H, Kaseno K, Miyazaki S, Shiomi Y, Tama N, Ikeda H, Ishida K, Uzui H, Ohno S, Horie M, Yokoyama O, Tada H.
  • Journal Title: J Am Heart Assoc. Volume: 10 Issue: 5
  • DOI: 10.1161/jaha.120.017267
  • Peer Reviewed / Open Access
• [Journal Article] Familial sick sinus syndrome possibly associated with novel SCN5A mutation diagnosed in pregnancy (2021)
  • Author(s): Abe Ichitaro、Wang Pu、Takahashi Masaki、Ohno Seiko、Ono Katsushige、Takahashi Naohiko
  • Journal Title: HeartRhythm Case Reports Volume: 7 Issue: 2 Pages: 117-122
  • DOI: 10.1016/j.hrcr.2020.11.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High Prevalence of Late-Appearing T-Wave in Patients With Long QT Syndrome Type 8 (2020)
  • Author(s): Fukuyama M, Ohno S,Ozawa J, Kato K, Makiyama T, Nakagawa Y, Horie M.
  • Journal Title: Circulation Journal Volume: 84 Issue: 4 Pages: 559-568
  • DOI: 10.1253/circj.CJ-19-1101
  • NAID: 130007815680
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-03-25
  • Peer Reviewed / Open Access
• [Journal Article] Co-Phenotype of Left Ventricular Non-Compaction Cardiomyopathy and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia in Association With R169Q, a <i>Ryanodine Receptor Type 2</i> Missense Mutation (2020)
  • Author(s): Nozaki Y, Kato Y, Uike K, Yamamura K, Kikuchi M, Yasuda M, Ohno S, Horie M, Murayama T, Kurebayashi N, Horigome H
  • Journal Title: Circulation Journal Volume: 84 Issue: 2 Pages: 226-234
  • DOI: 10.1253/circj.CJ-19-0720
  • NAID: 130007789920
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-01-24
  • Peer Reviewed / Open Access
• [Journal Article] Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls (2020)
  • Author(s): 2.Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, et al.
  • Journal Title: Genetics in Medicine Volume: 23 Issue: 1 Pages: 47-58
  • DOI: 10.1038/s41436-020-00946-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families (2020)
  • Author(s): 3.Wijeyeratne YD, Tanck MW, Mizusawa Y, Batchvarov V, Barc J, Crotti L, et al.
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 13 Issue: 6
  • DOI: 10.1161/circgen.120.002911
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SCN5A mutation identified in a patient with short-coupled variant of torsades de pointes (2020)
  • Author(s): Sonoda Keiko、Ohno Seiko、Shimizu Yukiko、Kaitani Kazuaki、Makiyama Takeru、Nakagawa Yoshihisa、Horie Minoru
  • Journal Title: Pacing and Clinical Electrophysiology Volume: - Issue: 5 Pages: 456-461
  • DOI: 10.1111/pace.13924
  • Peer Reviewed
• [Journal Article] Identification of transmembrane protein 168 mutation in familial Brugada syndrome. (2020)
  • Author(s): Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H.
  • Journal Title: FASEB Journal Volume: 34 Issue: 5 Pages: 6399-6417
  • DOI: 10.1096/fj.201902991r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An NGS-based genotyping in LQTS; minor genes are no longer minor (2020)
  • Author(s): Ohno Seiko、Ozawa Junichi、Fukuyama Megumi、Makiyama Takeru、Horie Minoru
  • Journal Title: Journal of Human Genetics Volume: 65 Issue: 12 Pages: 1083-1091
  • DOI: 10.1038/s10038-020-0805-z
  • Peer Reviewed / Open Access
• [Journal Article] Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome (2020)
  • Author(s): Lahrouchi N, Tadros R, Crotti L, Makiyama T et al.
  • Journal Title: Circulation Volume: 142 Issue: 4 Pages: 324-338
  • DOI: 10.1161/circulationaha.120.045956
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Postoperative supraventricular tachycardia and polymorphic ventricular tachycardia due to a novel SCN5A variant: a case report of a rare comorbidity that is difficult to diagnose (2020)
  • Author(s): Kato Koichi、Ozawa Tomoya、Ohno Seiko、Nakagawa Yoshihisa、Horie Minoru
  • Journal Title: BMC Cardiovascular Disorders Volume: 20 Issue: 1
  • DOI: 10.1186/s12872-020-01601-2
  • NAID: 120006871010
  • Peer Reviewed / Open Access
• [Journal Article] LMNA Missense Mutation Causes Nonsense-Mediated mRNA Decay and Severe Dilated Cardiomyopathy (2020)
  • Author(s): Kato Koichi、Ohno Seiko、Sonoda Keiko、Fukuyama Megumi、Makiyama Takeru、Ozawa Tomoya、Horie Minoru
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 13 Issue: 5 Pages: 435-443
  • DOI: 10.1161/circgen.119.002853
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Propranolol Attenuates Late Sodium Current in a Long QT Syndrome Type 3-Human Induced Pluripotent Stem Cell Model (2020)
  • Author(s): Hirose Sayako、Makiyama Takeru、Melgari Dario、Yamamoto Yuta、Wuriyanghai Yimin、Yokoi Fumika、Nishiuchi Suguru、Harita Takeshi、Hayano Mamoru、Kohjitani Hirohiko、Gao Jingshan、Kashiwa Asami、Nishikawa Misato、Wu Jie、Yoshimoto Jun、Chonabayashi Kazuhisa、Ohno Seiko、Yoshida Yoshinori、Horie Minoru、Kimura Takeshi
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 8 Pages: 761-761
  • DOI: 10.3389/fcell.2020.00761
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic QT Changes in Long QT Syndrome Type 8 (2019)
  • Author(s): Harada Mizuki、Suzuki Hiroshi、Ohno Seiko、Ozawa Junichi、Saitoh Akihiko、Horie Minoru
  • Journal Title: Circulation Journal Volume: 83 Issue: 7 Pages: 1614
  • DOI: 10.1253/circj.CJ-18-0984
  • NAID: 130007666938
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-06-25
  • Peer Reviewed / Open Access
• [Journal Article] Implantable cardioverter-defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest (2019)
  • Author(s): van der Werf Christian、Lieve Krystien V、Seiko Ohno、Leenhardt Antoine、Ackerman Michael J、Wilde Arthur A、et al.
  • Journal Title: European Heart Journal Volume: 40 Issue: 35 Pages: 2953-2961
  • DOI: 10.1093/eurheartj/ehz309
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A de novo gain-of-function KCND3 mutation in early repolarization syndrome (2019)
  • Author(s): Takayama Koichiro、Ohno Seiko、Ding Wei-Guang、Ashihara Takashi、Fukumoto Daisuke、Wada Yuko、Makiyama Takeru、Kise Hiroaki、Hoshiai Minako、Matsuura Hiroshi、Horie Minoru
  • Journal Title: Heart Rhythm Volume: 16 Issue: 11 Pages: 1698-1706
  • DOI: 10.1016/j.hrthm.2019.05.033
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients (2019)
  • Author(s): Shimizu Wataru、Makimoto Hisaki、Yamagata Kenichiro、Kamakura Tsukasa、Wada Mitsuru、Miyamoto Koji、Inoue-Yamada Yuko、Okamura Hideo、Ishibashi Kohei、Noda Takashi、Nagase Satoshi、Miyazaki Aya、Sakaguchi Heima、Shiraishi Isao、Makiyama Takeru、Ohno Seiko、Itoh Hideki、et al
  • Journal Title: JAMA Cardiology Volume: in press Issue: 3 Pages: 246-254
  • DOI: 10.1001/jamacardio.2018.4925
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long QT syndrome with a de novo CALM2 mutation in a 4‐year‐old boy (2019)
  • Author(s): Fujita Shuhei、Nakagawa Ryo、Futatani Takeshi、Igarashi Noboru、Fuchigami Takamasa、Saito Shinsuke、Ohno Seiko、Horie Minoru、Hatasaki Kiyoshi
  • Journal Title: Pediatrics International Volume: 61 Issue: 9 Pages: 852-858
  • DOI: 10.1111/ped.13959
  • Peer Reviewed / Open Access
• [Journal Article] Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry (2019)
  • Author(s): Crotti Lia、Spazzolini Carla、Tester David J、Ohno Seiko、Ackerman Michael J、Schwartz Peter J, et al.
  • Journal Title: European Heart Journal Volume: 40 Issue: 35 Pages: 2964-2975
  • DOI: 10.1093/eurheartj/ehz311
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation. (2019)
  • Author(s): Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
  • Journal Title: Circulation Volume: In press Issue: 18 Pages: 2157-2169
  • DOI: 10.1161/circulationaha.118.036761
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional cofactor Vgll2 is required for functional adaptations of skeletal muscle induced by chronic overload (2019)
  • Author(s): Honda Masahiko、Tsuchimochi Hirotsugu、Hitachi Keisuke、Ohno Seiko
  • Journal Title: Journal of Cellular Physiology Volume: 印刷中 Issue: 9 Pages: 15809-15824
  • DOI: 10.1002/jcp.28239
  • Peer Reviewed
• [Journal Article] Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia (2019)
  • Author(s): Dharmawan T, Nakajima T, Ohno S, Iizuka T, Tamura S, Kaneko Y, Horie M, Kurabayashi M.
  • Journal Title: Ann Noninvasive Electrocardiol Volume: - Issue: 3
  • DOI: 10.1111/anec.12623
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Manifestations and Long-Term Mortality in <i>Lamin A/C</i> Mutation Carriers From a Japanese Multicenter Registry (2018)
  • Author(s): 14.Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Kato K, Yamamoto Y, Doi T, Shizuta S, Onoue K, Yagihara N, Ishikawa T, Watanabe I, Kawakami H, Oginosawa Y, Murakoshi N, Nogami A, Aonuma K, Saito Y, Kimura T, Yasuda S, Makita N, Shimizu W, Horie M, Kusano K.
  • Journal Title: Circulation Journal Volume: 82 Issue: 11 Pages: 2707-2714
  • DOI: 10.1253/circj.CJ-18-0339
  • NAID: 40021697176
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-10-25
  • Peer Reviewed / Open Access
• [Journal Article] Differential Diagnosis Between Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome Type 1 ― Modified Schwartz Score ― (2018)
  • Author(s): Ozawa Junichi、Ohno Seiko、Fujii Yusuke、Makiyama Takeru、Suzuki Hiroshi、Saitoh Akihiko、Horie Minoru
  • Journal Title: Circulation Journal Volume: 82 Issue: 9 Pages: 2269-2276
  • DOI: 10.1253/circj.CJ-17-1032
  • NAID: 130007438837
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-08-24
  • Peer Reviewed / Open Access
• [Journal Article] Autonomic Function and QT Interval During Night-Time Sleep in Infant Long QT Syndrome (2018)
  • Author(s): Yoshinaga Masao、Kucho Yu、Ushinohama Hiroya、Ishikawa Yuichi、Ohno Seiko、Ogata Hiromitsu
  • Journal Title: Circulation Journal Volume: 82 Issue: 8 Pages: 2152-2159
  • DOI: 10.1253/circj.CJ-18-0048
  • NAID: 130007419286
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-07-25
  • Peer Reviewed / Open Access
• [Journal Article] Bradycardia Is a Specific Phenotype of Catecholaminergic Polymorphic Ventricular Tachycardia Induced by <i>RYR2</i> Mutations (2018)
  • Author(s): Miyata Kazuaki、Ohno Seiko、Itoh Hideki、Horie Minoru
  • Journal Title: Internal Medicine Volume: 57 Issue: 13 Pages: 1813-1817
  • DOI: 10.2169/internalmedicine.9843-17
  • NAID: 130007387124
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-07-01
  • Peer Reviewed / Open Access
• [Journal Article] Novel roles of Drosophila FUS and Aub responsible for piRNA biogenesis in neuronal disorders. (2018)
  • Author(s): Wakisaka KT, Tanaka R, Hirashima T, Muraoka Y, Azuma Y, Yoshida H, Tokuda T, Asada S, Suda K, Ichiyanagi K, Ohno S, Itoh M, Yamaguchi M.
  • Journal Title: Brain Res. Volume: 18 Pages: 30646-30652
  • DOI: 10.1016/j.brainres.2018.12.028
  • Peer Reviewed / Open Access
• [Journal Article] A challenge for mutation specific risk stratification in long QT syndrome type 1 (2018)
  • Author(s): Yagi Noriaki、Itoh Hideki、Hisamatsu Takashi、Tomita Yukinori、Kimura Hiromi、Fujii Yusuke、Makiyama Takeru、Horie Minoru、Ohno Seiko
  • Journal Title: Journal of Cardiology Volume: 18 Issue: 1 Pages: 30012-1
  • DOI: 10.1016/j.jjcc.2017.12.011
  • Peer Reviewed
• [Journal Article] Complex aberrant splicing in the induced pluripotent stem cell?derived cardiomyocytes from a patient with long QT syndrome carrying KCNQ1-A344Aspl mutation (2018)
  • Author(s): Wuriyanghai Yimin、Makiyama Takeru、Sasaki Kenichi、Kamakura Tsukasa、Yamamoto Yuta、Hayano Mamoru、Harita Takeshi、Nishiuchi Suguru、Chen Jiarong、Kohjitani Hirohiko、Hirose Sayako、Yokoi Fumika、Gao Jingshan、Chonabayashi Kazuhisa、Watanabe Ken、Ohno Seiko、Yoshida Yoshinori、Kimura Takeshi、Horie Minoru
  • Journal Title: Heart Rhythm Volume: 15 Issue: 10 Pages: 1566-1574
  • DOI: 10.1016/j.hrthm.2018.05.028
  • Peer Reviewed / Open Access
• [Journal Article] A hERG mutation E1039X produced a synergistic lesion on IKs together with KCNQ1-R174C mutation in a LQTS family with three compound mutations (2018)
  • Author(s): Wu Jie、Mizusawa Yuka、Ohno Seiko、Ding Wei-Guang、Higaki Takashi、Wang Qi、Kohjitani Hirohiko、Makiyama Takeru、Itoh Hideki、Toyoda Futoshi、James Andrew F.、Hancox Jules C.、Matsuura Hiroshi、Horie Minoru
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 3129-3129
  • DOI: 10.1038/s41598-018-21442-6
  • NAID: 120006529715
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of zygotic piRNAs derived from paternal P elements with hybrid dysgenesis in Drosophila melanogaster (2018)
  • Author(s): Wakisaka Keiko Tsuji、Ichiyanagi Kenji、Ohno Seiko、Itoh Masanobu
  • Journal Title: Mobile DNA Volume: 9 Issue: 1 Pages: 7-7
  • DOI: 10.1186/s13100-018-0110-y
  • Peer Reviewed / Open Access
• [Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. (2018)
  • Author(s): Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
  • Journal Title: Br. J. Clin. Pharmacol. Volume: - Issue: 6 Pages: 1301-1312
  • DOI: 10.1111/bcp.13561
  • Peer Reviewed / Open Access
• [Journal Article] Copy number variations of SCN5A in Brugada syndrome (2018)
  • Author(s): Sonoda Keiko、Ohno Seiko、Ozawa Junichi、Hayano Mamoru、Hattori Tetsuhisa、Kobori Atsushi、Yahata Mitsuhiko、Aburadani Isao、Watanabe Seiichi、Matsumoto Yuichi、Makiyama Takeru、Horie Minoru
  • Journal Title: Heart Rhythm Volume: - Issue: 8 Pages: 1179-1188
  • DOI: 10.1016/j.hrthm.2018.03.033
  • Peer Reviewed
• [Journal Article] Prediagnostic electrocardiographic and echocardiographic findings of biopsy‐proven hypertrophic cardiomyopathy (2018)
  • Author(s): Seki Shunji、Yamashita Erika、Tanoue Kazuyuki、Nuruki Norihito、Sonoda Masahiro、Ohno Seiko、Ishibashi‐Ueda Hatsue、Tanaka Yuji、Yoshinaga Masao
  • Journal Title: Journal of Arrhythmia Volume: 34 Issue: 6 Pages: 643-646
  • DOI: 10.1002/joa3.12110
  • Peer Reviewed
• [Journal Article] Three cases of catecholaminergic polymorphic ventricular tachycardia with prolonged QT intervals including two cases of compound mutations (2018)
  • Author(s): Saito Aki、Ohno Seiko、Nuruki Norihito、Nomura Yuichi、Horie Minoru、Yoshinaga Masao
  • Journal Title: Journal of Arrhythmia Volume: 34 Issue: 3 Pages: 291-293
  • DOI: 10.1002/joa3.12053
  • Peer Reviewed / Open Access
• [Journal Article] A novel CACNA1C mutation identified in a patient with Timothy syndrome without syndactyly exerts both marked loss-and-gain of function effects (2018)
  • Author(s): Ozawa Junichi、Ohno Seiko、Saito Hideki、Saitoh Akihiko、Matsuura Hiroshi、Horie Minoru
  • Journal Title: HeartRhythm Case Reports Volume: in press Issue: 7 Pages: 273-277
  • DOI: 10.1016/j.hrcr.2018.03.003
  • Peer Reviewed / Open Access
• [Journal Article] A tryptophan residue in the caffeine-binding site of the ryanodine receptor regulates Ca2+ sensitivity (2018)
  • Author(s): Murayama Takashi、Ogawa Haruo、Kurebayashi Nagomi、Ohno Seiko、Horie Minoru、Sakurai Takashi
  • Journal Title: Communications Biology Volume: 1 Issue: 1 Pages: 98-98
  • DOI: 10.1038/s42003-018-0103-x
  • Peer Reviewed / Open Access
• [Journal Article] Electrical storm in an infant with short-coupled variant of torsade de pointes (2018)
  • Author(s): Kise Hiroaki、Ohno Seiko、Kono Yosuke、Yoshizawa Masashi、Harama Daisuke、Okafuji Asami、Toda Takako、Koizumi Keiichi、Hoshiai Minako、Sugita Kanji、Horie Minoru
  • Journal Title: Journal of Arrhythmia Volume: 34 Issue: 3 Pages: 315-318
  • DOI: 10.1002/joa3.12071
  • Peer Reviewed / Open Access
• [Journal Article] Home blood pressure variability and subclinical atherosclerosis in multiple vascular beds: A population-based study (2018)
  • Author(s): Hisamatsu Takashi、Miura Katsuyuki、Ohkubo Takayoshi、Arima Hisatomi、Fujiyoshi Akira、Satoh Atsushi、Kadota Aya、Zaid Maryam、Takashima Naoyuki、Ohno Seiko、Horie Minoru、Ueshima Hirotsugu
  • Journal Title: Journal of Hypertension Volume: 36 Issue: 11 Pages: 2193
  • DOI: 10.1097/hjh.0000000000001810
  • Peer Reviewed / Open Access
• [Journal Article] Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome (2018)
  • Author(s): Fukumoto Daisuke、Ding Wei-Guang、Wada Yuko、Fujii Yusuke、Ichikawa Mari、Takayama Koichiro、Fukuyama Megumi、Kato Koichi、Itoh Hideki、Makiyama Takeru、Omatsu-Kanbe Mariko、Matsuura Hiroshi、Horie Minoru、Ohno Seiko
  • Journal Title: Journal of Cardiology Volume: 71 Issue: 4 Pages: 401-408
  • DOI: 10.1016/j.jjcc.2017.10.004
  • Peer Reviewed
• [Journal Article] Catecholaminergic polymorphic ventricular tachycardia managed as orthostatic dysregulation and epilepsy in 11‐ and 15‐year‐old sisters (2018)
  • Author(s): Fujita Shuhei、Nishida Keigo、Irabu Hitoshi、Nakagawa Ryo、Futatani Takeshi、Igarashi Noboru、Usuda Kazuo、Nagata Yoshiki、Ohno Seiko、Horie Minoru、Hatasaki Kiyoshi
  • Journal Title: Pediatrics International Volume: 60 Issue: 11 Pages: 998-1001
  • DOI: 10.1111/ped.13688
  • Peer Reviewed / Open Access
• [Presentation] Dynamic change in electrocardiogram in a neonate with HCN4 insertion mutation (2020)
  • Author(s): Ohno S, Kan N, Kato K, Ushinohama H, Horie M
  • Organizer: Heart Rhythm Society Meeting 2020
  • Int'l Joint Research
• [Presentation] Arrhythmogenic Right Ventricular Cardiomyopathy (2020)
  • Author(s): Ohno S
  • Organizer: APHRS Virtual Congress 2020
  • Int'l Joint Research / Invited
• [Presentation] An Update on the Diagnosis and Management of Catecholaminergic Polymorphic Ventricular Tachycardia (2020)
  • Author(s): Ohno S
  • Organizer: The 12th Annual Scientific Sessions of the Korean Heart Rhythm Society
  • Int'l Joint Research / Invited
• [Presentation] Long-read sequence confirmed a large deletion of MYH6 and MYH7 in a family with atrial septal defect (2020)
  • Author(s): K. Sonoda, S. Ohno, M. Horie
  • Organizer: ESC CONGRESS 2020 - The Digital Experience
  • Int'l Joint Research
• [Presentation] カテコラミン誘発性多形性心室頻拍におけるICD治療の実態 (2020)
  • Author(s): 大野聖子、高山幸一郎、園田桂子、福山恵、加藤浩一、堀江稔
  • Organizer: 第12回植込みデバイス関連冬季大会
• [Presentation] 遺伝子検査とその解釈 (2020)
  • Author(s): 大野聖子
  • Organizer: 第56回日本小児循環器学会総会・学術集会
  • Invited
• [Presentation] How to Utilize the Genetic Information in Arrhythmogenic Right Ventricular Cardiomyopathy (2020)
  • Author(s): 大野聖子
  • Organizer: 第85回日本循環器学会学術集会
  • Invited
• [Presentation] Variable Electrophysiological Characteristics of CACNA1C Mutations Identified in Patients with Long QT Syndrome Type 8 (2020)
  • Author(s): Wang Q , Sonoda K, Makiyama T, Ozawa J, Takayama K, Dimitar P, Horie M, Ohno S
  • Organizer: 第85回日本循環器学会学術集会
• [Presentation] Genomic Research in Arrhythmia (2020)
  • Author(s): Seiko Ohno
  • Organizer: 第84回日本循環器学会学術集会
  • Invited
• [Presentation] Mutation specific clinical characteristics in long QT syndrome type 8; severe phenotype in Timothy syndrome patients. (2019)
  • Author(s): Ohno S, Yoshinaga M, Ozawa J, Fukuyama M, Sato S, Kashiwa A, Yasuda K, Kaneko S, Nakau K, Inukai S, Makiyama T, Aiba T, Suzuki H, Horie M.
  • Organizer: European Society of Cardiology
  • Int'l Joint Research
• [Presentation] Ventricular septum defect can be a key for the early diagnosis of Brugada syndrome in young patients with SCN5A mutations. (2019)
  • Author(s): Ohno S, Ozawa J, Sonoda K, Makiyama T, Horie M.
  • Organizer: American Society of Human Genetics
  • Int'l Joint Research
• [Presentation] Sodium channel cardiomyopathy: genetic and clinical spectrum. (2019)
  • Author(s): Ohno S
  • Organizer: Asian Pacific Heart Rhythm Society
  • Int'l Joint Research / Invited
• [Presentation] Pathophysiological substrate & Risk Stratification (2019)
  • Author(s): Ohno S
  • Organizer: Asian Pacific Heart Rhythm Society
  • Int'l Joint Research / Invited
• [Presentation] Genetics in Brugada Syndrome (2019)
  • Author(s): Ohno S
  • Organizer: Annual Scientific Session of the KHRS
  • Invited
• [Presentation] An NGS-based genotyping in LQTS; minor genes are no longer minor (2019)
  • Author(s): Ohno S,, Ozawa J, Fukuyama M, Makiyama T, Horie M
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Genetic Background of ARVC (2019)
  • Author(s): Ohno S,, Sonoda K, Horie M.
  • Organizer: 第83回日本循環器学会学術集会
  • Invited
• [Presentation] Clinical use of genetic analysis for the inherited primary arrhythmia syndromes (2019)
  • Author(s): Ohno S
  • Organizer: 第83回日本循環器学会学術集会
  • Invited
• [Presentation] LQTS, Ventricular Arrhythmias and SCD Pathophysiology and Mechanisms Ion Channel Disorders (2018)
  • Author(s): Ohno S
  • Organizer: European Heart Rhythm Society Meeting 2018 in Barcelona
  • Int'l Joint Research / Invited
• [Presentation] VT/VF: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): From Bench to Bedside (2018)
  • Author(s): Ohno S
  • Organizer: Asian Pacific Heart Rhythm Society Meeting 2018 in Taiwan
  • Int'l Joint Research / Invited
• [Presentation] What is New in the Genetics of Arrhythmogenic Right Ventricular Cardiomyopathy? (2018)
  • Author(s): Ohno S
  • Organizer: Asian Pacific Heart Rhythm Society Meeting 2018 in Taiwan
  • Int'l Joint Research / Invited
• [Presentation] High Frequency of De Novo KCNJ2 Mutations in Andersen-Tawil Syndrome Patients (2018)
  • Author(s): Hattori T, Sonoda K, Horie M, Ohno S
  • Organizer: Asian Pacific Heart Rhythm Society Meeting 2018 in Taiwan
  • Int'l Joint Research
• [Presentation] Functional Change of an SCN5A Mutation Identified in the Patient with Short-Coupled Variant of Torsades de Pointes. (2018)
  • Author(s): Sonoda K, Ohno S,, Hattori T, Horie M,
  • Organizer: Asian Pacific Heart Rhythm Society Meeting 2018 in Taiwan
  • Int'l Joint Research
• [Presentation] Detection of Copy Number Variations by Next Generation Sequencer,a Missing Genetic Defect (2018)
  • Author(s): Ohno S,, Sonoda K, Ichikawa M, Yoshinaga M, Horie M.
  • Organizer: 第82回日本循環器学会学術集会
  • Invited
• [Presentation] Early Repolarization Syndrome Caused by a de novo KCND3 Gain-of-Function Mutation (2018)
  • Author(s): Takayama K, Ohno S,, Ding WG, Ashihara T, Kise H, Hoshiai M, Matsuura H, Horie M..
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Functional Analysis of Mutant Nav1.5 Channels Clarified Severe Phenotype of a Female Patient with Compound SCN5A Mutations. (2018)
  • Author(s): Fukumoto D, Ohno S,, Makiyama T, Kubo T, Kitaoka H, Matsuura H, Horie M.
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] 不整脈原性右室心筋症に特異的な遺伝子変異の病原性を考える (2018)
  • Author(s): 大野聖子、和田悠子、堀江稔
  • Organizer: 第4回日本心筋症研究会
• [Presentation] ゲノム医療を活用した不整脈診療 (2018)
  • Author(s): 大野聖子
  • Organizer: 第66回日本心臓病学会学術集会
  • Invited
• [Presentation] 遺伝性不整脈の遺伝子診断 (2018)
  • Author(s): 大野聖子
  • Organizer: 第22回日本心不全学会学術集会
  • Invited
• [Presentation] 不整脈を呈するCALM2変異キャリアの特徴 (2018)
  • Author(s): 大野聖子、中右弘一、真鍋博美、吉田葉子、青木寿明、藤田修平、牧山武、 堀江稔
  • Organizer: 第23回日本小児心電学会学術集会
• [Book] 循環器診療コンプリート 心筋症 「不整脈原性右室心筋症」 (2021)
  • Author(s): 大野聖子、北岡 裕章
  • Total Pages: 272
  • Publisher: 学研メディカル秀潤社
  • ISBN: 9784780904079
• [Book] 最新ガイドラインに基づく 循環器疾患 診療指針2021-'22 その他の遺伝性不整脈（CPVT, QT短縮症候群, PCCD, ARVC） (2020)
  • Author(s): 大野聖子、清水 渉
  • Total Pages: 384
  • Publisher: 総合医学社
  • ISBN: 9784883787241
• [Remarks] 国立循環器病研究センター 研究所 分子生物学部
  • URL: http://www.ncvc.go.jp/res/divisions/bioscience/
• [Remarks] 滋賀医科大学 循環器内科
  • URL: http://www.shiga-med.ac.jp/~hqmed1/research/