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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賴亮全(Liang-Chuan Lai) | |
dc.contributor.author | Ching-Yu Julius Chen | en |
dc.contributor.author | 陳璟毓 | zh_TW |
dc.date.accessioned | 2021-06-17T07:04:21Z | - |
dc.date.available | 2020-08-26 | |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-29 | |
dc.identifier.citation | 1. Antzelevitch C, Brugada P, Borggrefe M et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005;111:659-70.
2. Juang JM, Chen CY, Chen YH et al. Prevalence and prognosis of Brugada electrocardiogram patterns in an elderly Han Chinese population: a nation-wide community-based study (HALST cohort). Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2015;17 Suppl 2:ii54-62. 3. Priori SG, Wilde AA, Horie M et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932-63. 4. Sroubek J, Probst V, Mazzanti A et al. Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis. Circulation 2016;133:622-30. 5. Priori SG, Gasparini M, Napolitano C et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. Journal of the American College of Cardiology 2012;59:37-45. 6. Georgopoulos S, Letsas KP, Liu T et al. A meta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2018;20:134-139. 7. Manrai AK, Funke BH, Rehm HL et al. Genetic Misdiagnoses and the Potential for Health Disparities. The New England journal of medicine 2016;375:655-65. 8. Behr ER, Savio-Galimberti E, Barc J et al. Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study. Cardiovascular research 2015;106:520-9. 9. Mizusawa Y, Wilde AA. Brugada syndrome. Circulation Arrhythmia and electrophysiology 2012;5:606-16. 10. Juang J-MJ, Tsai C-T, Lin L-Y et al. Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan. Journal of the Formosan Medical Association 2013;in press; http://dx.doi.org/10.1016/j.jfma.2013.02.002. 11. Shimizu W, Matsuo K, Kokubo Y et al. Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome. J Cardiovasc Electrophysiol 2007;18:415-21. 12. Di Diego JM, Cordeiro JM, Goodrow RJ et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation 2002;106:2004-11. 13. Juang JM, Tsai CT, Lin LY et al. Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan. Journal of the Formosan Medical Association = Taiwan yi zhi 2015;114:620-6. 14. Hu D, Barajas-Martinez H, Pfeiffer R et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. Journal of the American College of Cardiology 2014;64:66-79. 15. Fukuyama M, Ohno S, Makiyama T, Horie M. Novel SCN10A variants associated with Brugada syndrome. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2016;18:905-11. 16. Bayes de Luna A, Brugada J, Baranchuk A et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. Journal of electrocardiology 2012;45:433-42. 17. Chevallier S, Forclaz A, Tenkorang J et al. New electrocardiographic criteria for discriminating between Brugada types 2 and 3 patterns and incomplete right bundle branch block. Journal of the American College of Cardiology 2011;58:2290-8. 18. Serra G, Baranchuk A, Bayes-De-Luna A et al. New electrocardiographic criteria to differentiate the Type-2 Brugada pattern from electrocardiogram of healthy athletes with r'-wave in leads V1/V2. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2014. 19. Postema PG. Are we able to predict the diagnosis of Brugada syndrome? Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2014;16:1543-5. 20. Miyasaka Y, Tsuji H, Yamada K et al. Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan. Journal of the American College of Cardiology 2001;38:771-4. 21. Uhm JS, Hwang IU, Oh YS et al. Prevalence of electrocardiographic findings suggestive of sudden cardiac death risk in 10,867 apparently healthy young Korean men. Pacing and clinical electrophysiology : PACE 2011;34:717-23. 22. Tsuji H, Sato T, Morisaki K, Iwasaka T. Prognosis of subjects with Brugada-type electrocardiogram in a population of middle-aged Japanese diagnosed during a health examination. The American journal of cardiology 2008;102:584-7. 23. Priori SG, Wilde AA, Horie M et al. Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Europace 2013;15:1389-406. 24. Kapplinger JD, Tester DJ, Alders M et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart rhythm : the official journal of the Heart Rhythm Society 2010;7:33-46. 25. Fernandez-Falgueras A, Sarquella-Brugada G, Brugada J, Brugada R, Campuzano O. Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances. Biology 2017;6. 26. Hosseini SM, Kim R, Udupa S et al. Reappraisal of Reported Genes for Sudden Arrhythmic Death. Circulation 2018;138:1195-1205. 27. Lek M, Karczewski KJ, Minikel EV et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016;536:285-91. 28. Priori SG, Napolitano C, Gasparini M et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000;102:2509-15. 29. Hong K, Brugada J, Oliva A et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004;110:3023-7. 30. Fan CT, Lin JC, Lee CH. Taiwan Biobank: a project aiming to aid Taiwan's transition into a biomedical island. Pharmacogenomics 2008;9:235-46. 31. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine : official journal of the American College of Medical Genetics 2015;17:405-24. 32. Milman A, Andorin A, Gourraud JB et al. Age of First Arrhythmic Event in Brugada Syndrome: Data From the SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) in 678 Patients. Circulation Arrhythmia and electrophysiology 2017;10. 33. Sieira J, Conte G, Ciconte G et al. Clinical characterisation and long-term prognosis of women with Brugada syndrome. Heart 2016;102:452-8. 34. Vrtovec B, Delgado R, Zewail A, Thomas CD, Richartz BM, Radovancevic B. Prolonged QTc interval and high B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure. Circulation 2003;107:1764-9. 35. Newton-Cheh C, Larson MG, Corey DC et al. QT interval is a heritable quantitative trait with evidence of linkage to chromosome 3 in a genome-wide linkage analysis: The Framingham Heart Study. Heart rhythm : the official journal of the Heart Rhythm Society 2005;2:277-84. 36. Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J. QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation 1991;84:1516-23. 37. Tomaselli GF, Beuckelmann DJ, Calkins HG et al. Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 1994;90:2534-9. 38. Straus SM, Kors JA, De Bruin ML et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol 2006;47:362-7. 39. Liu XK, Katchman A, Drici MD et al. Gender difference in the cycle length-dependent QT and potassium currents in rabbits. The Journal of pharmacology and experimental therapeutics 1998;285:672-9. 40. Abi-Gerges N, Small BG, Lawrence CL, Hammond TG, Valentin JP, Pollard CE. Gender differences in the slow delayed (IKs) but not in inward (IK1) rectifier K+ currents of canine Purkinje fibre cardiac action potential: key roles for IKs, beta-adrenoceptor stimulation, pacing rate and gender. British journal of pharmacology 2006;147:653-60. 41. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 1996;94:1471-4. 42. Liu XK, Katchman A, Whitfield BH et al. In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits. Cardiovascular research 2003;57:28-36. 43. Aizawa Y, Fujisawa T, Katsumata Y et al. Sex-Dependent Phenotypic Variability of an SCN5A Mutation: Brugada Syndrome and Sick Sinus Syndrome. Journal of the American Heart Association 2018;7:e009387. 44. Smits JP, Eckardt L, Probst V et al. Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. Journal of the American College of Cardiology 2002;40:350-6. 45. Benito B, Sarkozy A, Mont L et al. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol 2008;52:1567-73. 46. Maury P, Rollin A, Sacher F et al. Prevalence and prognostic role of various conduction disturbances in patients with the Brugada syndrome. The American journal of cardiology 2013;112:1384-9. 47. Shimizu N, Iwamoto M, Nakano Y et al. Long-term electrocardiographic follow-up from childhood of an adult patient with Brugada syndrome associated with sick sinus syndrome. Circulation journal : official journal of the Japanese Circulation Society 2009;73:575-9. 48. Meregalli PG, Tan HL, Probst V et al. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart rhythm : the official journal of the Heart Rhythm Society 2009;6:341-8. 49. Landrum MJ, Lee JM, Benson M et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 2016;44:D862-8. 50. Stenson PD, Ball EV, Mort M, Phillips AD, Shaw K, Cooper DN. The Human Gene Mutation Database (HGMD) and its exploitation in the fields of personalized genomics and molecular evolution. Curr Protoc Bioinformatics 2012;Chapter 1:Unit1 13. 51. Nagasaki M, Yasuda J, Katsuoka F et al. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nature communications 2015;6:8018. 52. Whiffin N, Minikel E, Walsh R et al. Using high-resolution variant frequencies to empower clinical genome interpretation. Genetics in medicine : official journal of the American College of Medical Genetics 2017. 53. Juang JJ, Horie M. Genetics of Brugada syndrome. Journal of arrhythmia 2016;32:418-425. 54. Matsusue A, Yuasa I, Umetsu K et al. The global distribution of the p.R1193Q polymorphism in the SCN5A gene. Leg Med (Tokyo) 2016;19:72-6. 55. Wu CK, Juang JJ, Chiang JY, Li YH, Tsai CT, Chiang FT. The Taiwan Heart Registries: Its Influence on Cardiovascular Patient Care. Journal of the American College of Cardiology 2018;71:1273-1283. 56. Antzelevitch C, Brugada P, Borggrefe M et al. Brugada syndrome: report of the second consensus conference. Heart rhythm : the official journal of the Heart Rhythm Society 2005;2:429-40. 57. Antzelevitch C. The Brugada syndrome: ionic basis and arrhythmia mechanisms. Journal of cardiovascular electrophysiology 2001;12:268-72. 58. Vatta M, Dumaine R, Varghese G et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet 2002;11:337-45. 59. Le Scouarnec S, Karakachoff M, Gourraud JB et al. Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. Hum Mol Genet 2015;24:2757-63. 60. Tan BY, Yong RY, Barajas-Martinez H et al. A Brugada syndrome proband with compound heterozygote SCN5A mutations identified from a Chinese family in Singapore. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2016;18:897-904. 61. Samani K, Wu G, Ai T et al. A novel SCN5A mutation V1340I in Brugada syndrome augmenting arrhythmias during febrile illness. Heart rhythm : the official journal of the Heart Rhythm Society 2009;6:1318-26. 62. Cerrone M, Lin X, Zhang M et al. Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype. Circulation 2014;129:1092-103. 63. Marangoni S, Di Resta C, Rocchetti M et al. A Brugada syndrome mutation (p.S216L) and its modulation by p.H558R polymorphism: standard and dynamic characterization. Cardiovascular research 2011;91:606-16. 64. Fraser HB, Lam LL, Neumann SM, Kobor MS. Population-specificity of human DNA methylation. Genome biology 2012;13:R8. 65. Abriel H. Genetic background of Brugada syndrome is more complex than what we would like it to be! Cardiovascular research 2015;106:351-2. 66. Bezzina CR, Barc J, Mizusawa Y et al. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nat Genet 2013;45:1044-9. 67. Juang JM, Lu TP, Lai LC et al. Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome. Sci Rep 2014;4:6733. 68. Lee S, Wu MC, Lin X. Optimal tests for rare variant effects in sequencing association studies. Biostatistics 2012;13:762-75. 69. Lee S, Emond MJ, Bamshad MJ et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. American journal of human genetics 2012;91:224-37. 70. Chen CJ, Lu TP, Lin LY et al. Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry. Frontiers in genetics 2018;9:680. 71. Ioannidis NM, Rothstein JH, Pejaver V et al. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. American journal of human genetics 2016;99:877-885. 72. Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nature genetics 2014;46:310-5. 73. Shihab HA, Gough J, Cooper DN et al. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Human mutation 2013;34:57-65. 74. Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nature methods 2014;11:361-2. 75. Antzelevitch C. Genetic, molecular and cellular mechanisms underlying the J wave syndromes. Circulation journal : official journal of the Japanese Circulation Society 2012;76:1054-65. 76. Kapplinger JD, Tester DJ, Alders M et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart rhythm : the official journal of the Heart Rhythm Society 2010;7:33-46. 77. Hu D, Barajas-Martinez H, Terzic A et al. ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene. International journal of cardiology 2014;171:431-42. 78. Burashnikov E, Pfeiffer R, Barajas-Martinez H et al. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart rhythm : the official journal of the Heart Rhythm Society 2010;7:1872-82. 79. Crotti L, Marcou CA, Tester DJ et al. Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing. Journal of the American College of Cardiology 2012;60:1410-8. 80. Selga E, Campuzano O, Pinsach-Abuin ML et al. Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort. PloS one 2015;10:e0132888. 81. Ishikawa T, Takahashi N, Ohno S et al. Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5. Circulation journal : official journal of the Japanese Circulation Society 2013;77:959-67. 82. Priori SG, Napolitano C, Gasparini M et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002;105:1342-7. 83. Watanabe H, Ohkubo K, Watanabe I et al. SCN5A mutation associated with ventricular fibrillation, early repolarization, and concealed myocardial abnormalities. International journal of cardiology 2013;165:e21-3. 84. Ishikawa T, Sato A, Marcou CA et al. A novel disease gene for Brugada syndrome: sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5. Circulation Arrhythmia and electrophysiology 2012;5:1098-107. 85. Rook MB, Bezzina Alshinawi C, Groenewegen WA et al. Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovascular research 1999;44:507-17. 86. Matsuo K, Akahoshi M, Nakashima E et al. The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: a population-based study of four decades. Journal of the American College of Cardiology 2001;38:765-70. 87. Tohyou Y, Nakazawa K, Takenobu H, Akagi T, Miyake H, Murayama M. A survey in the incidence of right bundle branch block with ST elevation among normal population. Jpn J Electrocardiol 1995;15:223-226. 88. Atarashi H, Ogawa S, Harumi K et al. Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads: Japanese Registry of Brugada Syndrome. Idiopathic Ventricular Fibrillation Investigators. Journal of the American College of Cardiology 2001;37:1916-20. 89. Furuhashi M, Uno K, Tsuchihashi K et al. Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population. Heart 2001;86:161-166. 90. Sakabe M, Fujiki A, Tani M, Nishida K, Mizumaki K, Inoue H. Proportion and prognosis of healthy people with coved or saddle-back type ST segment elevation in the right precordial leads during 10 years follow-up. European heart journal 2003;24:1488-93. 91. Oe H, Takagi M, Tanaka A et al. Prevalence and clinical course of the juveniles with Brugada-type ECG in Japanese population. Pacing and clinical electrophysiology : PACE 2005;28:549-54. 92. Ito H, Yano K, Chen R, He Q, Curb JD. The prevalence and prognosis of a Brugada-type electrocardiogram in a population of middle-aged Japanese-American men with follow-up of three decades. The American journal of the medical sciences 2006;331:25-9. 93. Shin SC, Ryu HM, Lee JH et al. Prevalence of the Brugada-type ECG recorded from higher intercostal spaces in healthy Korean males. Circulation journal : official journal of the Japanese Circulation Society 2005;69:1064-7. 94. Gervacio-Domingo G, Isidro J, Tirona J et al. The Brugada type 1 electrocardiographic pattern is common among Filipinos. 2008;61:1067-1072. 95. Wajed A, Aslam Z, Abbas SF et al. Frequency of Brugada-type ECG pattern (Brugada sign) in an apparently healthy young population. Journal of Ayub Medical College, Abbottabad : JAMC 2008;20:121-4. 96. Hermida JS, Lemoine JL, Aoun FB, Jarry G, Rey JL, Quiret JC. Prevalence of the brugada syndrome in an apparently healthy population. The American journal of cardiology 2000;86:91-4. 97. Blangy H, Sadoul N, Coutelour JM et al. [Prevalence of Brugada syndrome among 35,309 inhabitants of Lorraine screened at a preventive medicine centre]. Archives des maladies du coeur et des vaisseaux 2005;98:175-80. 98. Junttila MJ, Raatikainen MJ, Karjalainen J, Kauma H, Kesaniemi YA, Huikuri HV. Prevalence and prognosis of subjects with Brugada-type ECG pattern in a young and middle-aged Finnish population. European heart journal 2004;25:874-8. 99. Bozkurt A, Yas D, Seydaoglu G, Acarturk E. Frequency of Brugada-type ECG pattern (Brugada sign) in Southern Turkey. International heart journal 2006;47:541-7. 100. Pecini R, Cedergreen P, Theilade S, Haunso S, Theilade J, Jensen GB. The prevalence and relevance of the Brugada-type electrocardiogram in the Danish general population: data from the Copenhagen City Heart Study. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2010;12:982-6. 101. Gallagher MM, Forleo GB, Behr ER et al. Prevalence and significance of Brugada-type ECG in 12,012 apparently healthy European subjects. International journal of cardiology 2008;130:44-8. 102. Sinner MF, Pfeufer A, Perz S et al. Spontaneous Brugada electrocardiogram patterns are rare in the German general population: results from the KORA study. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2009;11:1338-44. 103. Schukro C, Berger T, Stix G et al. Regional prevalence and clinical benefit of implantable cardioverter defibrillators in Brugada syndrome. International journal of cardiology 2010;144:191-4. 104. Lee C, Soni A, Tate RB, Cuddy TE. The incidence and prognosis of Brugada electrocardiographic pattern in the Manitoba Follow-Up Study. The Canadian journal of cardiology 2005;21:1286-90. 105. Juang JM, Phan WL, Chen PC et al. Brugada-type electrocardiogram in the Taiwanese population--is it a risk factor for sudden death? Journal of the Formosan Medical Association = Taiwan yi zhi 2011;110:230-8. 106. Viskin S, Fish R, Eldar M et al. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls. Heart 2000;84:31-6. 107. Letsas KP, Gavrielatos G, Efremidis M et al. Prevalence of Brugada sign in a Greek tertiary hospital population. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2007;9:1077-80. 108. Monroe MH, Littmann L. Two-year case collection of the Brugada syndrome electrocardiogram pattern at a large teaching hospital. Clinical cardiology 2000;23:849-51. 109. Greer RW, Glancy DL. Prevalence of the Brugada electrocardiographic pattern at the Medical Center of Louisiana in New Orleans. J La State Med Soc 2003;155:242-6. 110. Donohue D, Tehrani F, Jamehdor R, Lam C, Movahed MR. The prevalence of Brugada ECG in adult patients in a large university hospital in the western United States. The American heart hospital journal 2008;6:48-50. 111. Patel SS, Anees S, Ferrick KJ. Prevalence of a Brugada pattern electrocardiogram in an urban population in the United States. Pacing and clinical electrophysiology : PACE 2009;32:704-8. 112. Mohammed A, Amir A, Sameh S, Magdi M. Low prevalence of Brugada-type electrocardiogram in a prospective large cohort of Egyptians. The Egyptian Heart J 2013;65:259-263. 113. Beziau DM, Barc J, O'Hara T et al. Complex Brugada syndrome inheritance in a family harbouring compound SCN5A and CACNA1C mutations. Basic research in cardiology 2014;109:446. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72717 | - |
dc.description.abstract | 布魯蓋達症候群 (Brugada syndrome, BrS) 是一種體顯性遺傳性疾病,病患可能會因心室顫動而猝死。據統計,在心因性猝死 (sudden cardiac death, SCD) 的病患中,約4%是由此病所致。此病好發於東南亞,盛行率約0.12%,而在台灣亦不少見,目前我們研究團隊的收案人數已達到全亞洲最多。為了避免憾事的發生,了解台灣的現況並找出高危險群是至關重要的。
布魯蓋達症候群的猝死好發於40歲前後,因此對於年輕人要積極做危險性分級 (risk stratification),在高風險的病患裝設植入性心臟整流去顫器 (implantable cardioverter-defibrillator, ICD) 可以防止猝死。然而,年長病患的風險是否仍高,是否也需要同等積極,目前相關的研究並不多。我們從5,214位健康年長者(平均69.3歲)的心電圖中發現,典型第一型Brugada心電圖的盛行率為0.077%,而無論是用HRS/EHRA/APHRS還是ISHNE的心電圖標準,有Brugada型心電圖的病患在四年的追蹤期間並沒有較高的死亡率,表示如果在無症狀的年長者身上發現Brugada型心電圖應該不用太擔心。 另外,布魯蓋達症候群好發於男性,男女比約9比1,目前認為跟性荷爾蒙對離子通道的調控有關,我們想知道會不會因此影響女性布魯蓋達症候群的危險度。因為男女人數的懸殊差異,過去的研究結果大多反映了男性布魯蓋達症候群的特徵,並不能直接套用在女性身上,於是我們嘗試比較台灣的布魯蓋達症候群中男女間的差異,發現雖然猝死或暈厥的發生率沒有差異,但女性病患會在較年輕的歲數發生暈厥,且女性較常會有猝死的家族病史和有較長的QTc,而發生猝死或暈厥的女性病患的心跳略慢於無症狀者。因此,女性的布魯蓋達症候群要更積極進行危險性分級,對於心跳慢者要提高警覺,並且要注意她們的家族中是否有潛在病患。 因為布魯蓋達症候群會遺傳,所以對家族成員進行篩檢是必要的,如此可以找出潛在的病患並預防猝死。家族篩檢的工具除了心電圖外,基因檢測也很重要,其中判斷變異 (variant) 的致病性相當關鍵。過去發現比較確定會致病的變異主要是出現在SCN5A這個基因上面,而一些疾病資料庫如ClinVar和HGMD (the Human Gene Mutation Database) 會對過去曾發表過的變異進行致病性的評比。隨著定序技術的發展和普及化,我們可以在網路上查詢到某一變異在許多地區和國家的盛行率,大家開始意識到種族之間的基因多樣性。我們發現一些過去認為罕見且會致病的變異其實在某些種族是很常見的,尤其是SCN5A以外的基因變異,必須重新檢視其致病性。此結果突顯了各種族大型生物資料庫的重要性,並且在評估一個基因變異的致病性時應多方參考其在各種族的盛行率。 雖然SCN5A是目前公認和布魯蓋達症候群最相關的基因,但根據我們的研究,台灣的布魯蓋達症候群病患中只有16.5%可以找到SCN5A的致病變異。如能找到其他與此病相關的基因將有助於家族篩檢。即使過去有許多研究認為尚有其他基因和此病有關,但它們的重要性仍存在爭議。SCN10A是近幾年認為和此病相關的重要基因,發現是透過和SCN5A的互動影響鈉電流。我們利用SKAT-O的計算發現SCN10A的罕見變異 (rare variants, allele frequencies < 1%) 在病患的盛行率明顯高於正常人,顯示其在台灣布魯蓋達症候群的重要致病角色。而我們在3.4%的病患身上找到SCN10A的致病變異,代表這樣的變異並不少見,值得篩檢。 根據上面的研究結果,我們提供在台灣的年長和女性布魯蓋達症候群病患的表現及危險性評估資料,也發現在判斷一個基因變異的致病性時應注意其在其他種族的盛行率。另外,SCN10A對於此病扮演著重要的角色,除了該列入常規篩檢的基因項目,也值得進一步探索其致病機轉。 | zh_TW |
dc.description.abstract | Brugada syndrome (BrS) is an inheritable arrhythmic disease with a hereditary pattern of autosomal dominance, which could cause ventricular fibrillation and lead to sudden death. It accounts for 4% of sudden cardiac death (SCD). It has the highest prevalence in the Southeast Asia, about 0.12%, and it is also not uncommon in Taiwan. In order to prevent the tragedy, the prevalence and characteristics of the patients with BrS in Taiwan should be investigated, as well as identification of the high-risk population.
The mean age of SCD attributed to BrS is around 40 years old. Thus, risk stratification in the young patients should be done aggressively, and implantable cardioverter-defibrillator (ICD) may prevent SCD in high-risk population. However, it is unclear that if the elderly patients also have the risk of SCD, and if an aggressive attitude is still necessary. In a cohort of 5,214 apparently healthy elders (mean 69.3 years old), I found 4 participants (0.077%) with typical type 1 Brugada electrocardiographic pattern (BrP), and the elders with BrP by either the criteria from HRS/EHRA/APHRS or ISHNE didn't have a higher mortality rate than those without BrP in the 4-year follow-up. It seems that BrP in the apparently healthy elders is relatively benign. Furthermore, most patients with BrS are male (male : female = 9 : 1), which is thought to be related to the impact of sexual hormones on the ion channels, and I am interested that if it may also have a prognostic effect in female BrS. Because of the male predominance, most of the past studies reflected the characteristics of male BrS, which could not apply on the female BrS. Therefore, I tried to compare the gender differences of BrS in Taiwan. Although there was no difference in the risk of SCD or syncope between genders, females suffered from syncope earlier than males and had a longer QTc, and the percentage of family history of SCD in females was slightly higher than males. Besides, the females with SCD or syncope had a slightly slower heart rate than those with no or mild symptom. As a result, female BrS deserves more medical attention, especially the female patients with low heart rate, and the potential patients among their family members should be discovered. Because of the heritability of BrS, it is necessary to do family screening in order to find out the potential patients and prevent SCD. Along with electrocardiograms, genetic screening is of class I recommendation, and the way to determine the pathogenicity of a variant is crucial. Currently, the most relevant gene is SCN5A, and several disease databases including ClinVar and HGMD (the Human Gene Mutation Database) analyzed the pathogenicity of the variants reported before. As the technique of sequencing improves and becomes available, the allele frequency of a variant among many areas and countries could be obtained via internet, and it is evident that there is the genetic diversity among ancestries. I found that several previously reported pathogenic rare variants were relative common in some ancestries, especially non-SCN5A variants, whose pathogenicity should be reassessed. This finding emphasized the importance of the large-scaled reference in every ancestry, and the allele frequencies of a variant in different ancestries should be taken into account when determining its pathogenicity. Although SCN5A is currently the most relevant gene in BrS, there were only 16.5% of Taiwanese patients with BrS having SCN5A causative variants according to my study. It is of great value in family screening if other relevant genes could be found. However, several genes reported to be associated with BrS are still controversial. SCN10A is a relevant gene appealing many attentions in these years, which could interact with SCN5A and influence the sodium current. I used the SKAT-O algorithm and found that rare variants (allele frequencies < 1%) of SCN10A were significantly enriched in the BrS patients, which implied the pathogenic role in BrS in Taiwan. Moreover, there were 3.4% of the patients having SCN10A causative variants, which was not uncommon and deserved for screening. According to the above findings, I provided the characteristics and prognosis of the elderly and female patients with BrS in Taiwan, and revealed the importance of allele frequencies of a variant among the thorought ancestries when judging its pathogenicity. Besides, SCN10A has an important role in BrS, and it should be included in the screening panel and deserves further investigation for the mechanism of pathogenesis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:04:21Z (GMT). No. of bitstreams: 1 ntu-108-D04441001-1.pdf: 3352547 bytes, checksum: c5ad4e1f5586830dd2b6eecb4c509e4f (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | Committee Approval i
List of Tables iv List of Figures v Acknowledgement vii 摘要 ix Abstract xi Abbreviation xiv General Introduction 1 Chapter 1: Prognostic study on elderly Brugada syndrome 3 Methods 3 Results 5 Discussion 7 Chapter 2: The characteristics of female Brugada syndrome 10 Methods 10 Results 13 Discussion 15 Chapter 3: Reassessment of the previously reported pathogenic variants of Brugada syndrome 18 Methods 18 Results 20 Discussion 22 Chapter 4: The prevalence and in silico analysis of SCN10A variants of Brugada syndrome 28 Methods 28 Results 30 Discussion 32 Clinical Implications and Future works 37 Conclusions 39 References 40 Tables 49 Figures 64 Supplementary Tables 76 Supplementary Figure 96 | |
dc.language.iso | en | |
dc.title | 布魯蓋達症候群—找出高危險群 | zh_TW |
dc.title | Study on Brugada Syndrome—Identification of high-risk population | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 江福田(Fu-Tien Chiang) | |
dc.contributor.oralexamcommittee | 莊志明(Jyh-Ming Juang),賴凌平(Ling-Ping Lai),盧子彬(Tzu-Pin Lu) | |
dc.subject.keyword | 布魯蓋達症候群,心因性猝死,危險性分級,性別差異,家族篩檢,SCN10A,SKAT-O, | zh_TW |
dc.subject.keyword | Brugada syndrome,sudden cardiac death,risk stratification,gender differences,family screening,SCN10A,SKAT-O, | en |
dc.relation.page | 96 | |
dc.identifier.doi | 10.6342/NTU201902002 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-29 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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