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{{Brugada syndrome}}
{{Brugada syndrome}}
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==Overview==
==Overview==
Approximately 20% of persons with Brugada syndrome have a [[mutation]] in the gene [[SCN5A]]. This [[gene]] [[Encoding (memory)|encodes]] for the [[sodium]] ion channel. The [[mutation]] is inherited in an [[autosomal dominant]] pattern, and is more commonly seen in [[Male|males]]. Brugada syndrome has also been shown to result from defects in a [[calcium]] channel.
==Pathophysiology==
==Pathophysiology==
===Genetics===
 
Approximately 20% of the cases of Brugada syndrome have been shown to be associated with mutation(s) in the [[gene]] that encodes for the [[sodium]] [[ion channel]] in the [[cell (biology)|cell]] [[cell membrane|membrane]]s of the muscle cells of the heart (the [[myocyte]]s). The gene, named [[SCN5A]], is located on the short arm of the third [[chromosome]] (3p21). Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural and epicardial dispersion of repolarization. The transmural dispersion underlies ST-segment elevation and the development of a vulnerable window across the ventricular wall, whereas the epicardial dispersion of repolarization facilitates the development of phase 2 reentry, which generates a phase 2 reentrant extrasystole that captures the vulnerable window to precipitate ventricular tachycardia and/or fibrillation that often results in sudden cardiac death. At present time however, all the reported patients died because of the disease and submitted to detailed necropsy study, have shown a structural right ventricular pathology underlying the syndrome.
* Approximately 20% of the cases of Brugada syndrome have been shown to be associated with [[mutation]](s) in the [[gene]] that [[Encoding (memory)|encodes]] for the [[sodium]] [[ion channel]] in the [[cell (biology)|cell]] [[cell membrane|membrane]]s of the muscle cells of the heart (the [[myocyte]]s). The [[gene]], named [[SCN5A]], is located on the short arm of the third [[chromosome]] (3p21).<ref name="LehnartAckerman2007">{{cite journal|last1=Lehnart|first1=Stephan E.|last2=Ackerman|first2=Michael J.|last3=Benson|first3=D. Woodrow|last4=Brugada|first4=Ramon|last5=Clancy|first5=Colleen E.|last6=Donahue|first6=J. Kevin|last7=George|first7=Alfred L.|last8=Grant|first8=Augustus O.|last9=Groft|first9=Stephen C.|last10=January|first10=Craig T.|last11=Lathrop|first11=David A.|last12=Lederer|first12=W. Jonathan|last13=Makielski|first13=Jonathan C.|last14=Mohler|first14=Peter J.|last15=Moss|first15=Arthur|last16=Nerbonne|first16=Jeanne M.|last17=Olson|first17=Timothy M.|last18=Przywara|first18=Dennis A.|last19=Towbin|first19=Jeffrey A.|last20=Wang|first20=Lan-Hsiang|last21=Marks|first21=Andrew R.|title=Inherited Arrhythmias|journal=Circulation|volume=116|issue=20|year=2007|pages=2325–2345|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.107.711689}}</ref>
* Loss-of-function [[Mutation|mutations]] in this [[gene]] lead to a loss of the action potential dome of some [[epicardial]] areas of the right [[ventricle]]. This results in [[Transmural care|transmural]] and [[epicardial]] dispersion of [[repolarization]]. The transmural dispersion underlies ST-segment elevation and the development of a vulnerable window across the [[Ventricle (heart)|ventricular]] wall, whereas the [[epicardial]] dispersion of [[repolarization]] facilitates the development of phase 2 reentry, which generates a phase 2 reentrant extrasystole that captures the vulnerable window to precipitate [[Ventricle (heart)|ventricular]] [[tachycardia]] and/or [[fibrillation]] that often results in sudden [[cardiac]] death.<ref name="DelpónCordeiro2008">{{cite journal|last1=Delpón|first1=Eva|last2=Cordeiro|first2=Jonathan M.|last3=Núñez|first3=Lucía|last4=Thomsen|first4=Poul Erik Bloch|last5=Guerchicoff|first5=Alejandra|last6=Pollevick|first6=Guido D.|last7=Wu|first7=Yuesheng|last8=Kanters|first8=J�rgen K.|last9=Larsen|first9=Carsten Toftager|last10=Hofman-Bang|first10=Jacob|last11=Burashnikov|first11=Elena|last12=Christiansen|first12=Michael|last13=Antzelevitch|first13=Charles|title=
            Functional Effects of
            KCNE3
            Mutation and Its Role in the Development of Brugada Syndrome
          |journal=Circulation: Arrhythmia and Electrophysiology|volume=1|issue=3|year=2008|pages=209–218|issn=1941-3149|doi=10.1161/CIRCEP.107.748103}}</ref><ref name="Bueno-OrovioCherry2015">{{cite journal|last1=Bueno-Orovio|first1=Alfonso|last2=Cherry|first2=Elizabeth M.|last3=Evans|first3=Steven J.|last4=Fenton|first4=Flavio H.|title=Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome|journal=BioMed Research International|volume=2015|year=2015|pages=1–12|issn=2314-6133|doi=10.1155/2015/197586}}</ref>


{| class="wikitable"
{| class="wikitable"
| '''Type''' || '''OMIM''' || '''Mutation''' || '''Notes'''
|'''Type'''||'''OMIM'''||'''Mutation'''||'''Notes'''
  |-  
  |-  
  | B1 || {{OMIM2|601144}} || alpha subunit of the [[sodium channel]] ([[SCN5A]]) || Current through this channel is commonly referred to as I<sub>Na</sub>. Gain of this channel leads to an unopposed Ito current ([[KCND2]])  
  | B1 ||{{OMIM2|601144}}|| alpha subunit of the [[sodium channel]] ([[SCN5A]]) || Current through this channel is commonly referred to as I<sub>Na</sub>. Gain of this channel leads to an unopposed Ito current ([[KCND2]])
  |-  
  |-  
  | B2 || {{OMIM2|611778}} || [[GPD1L]], Glycerol-3-phosphate dehydrogenase like peptide||  
  | B2 ||{{OMIM2|611778}}||[[GPD1L]], Glycerol-3-[[phosphate]] [[dehydrogenase]] like peptide||  
  |-  
  |-  
  | B3 || {{OMIM2|114205}} || [[CACNA1C]] || Alpha subunit of cardiac L-type calcium channel.<ref name="pmid 17224476">{{cite journal |author= Antzelevitch C, Pollevick GD, Cordeiro JM, et al  |title= Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death |journal=Circulation |volume=115 |issue=4 |pages=442–229 |year=2007 |pmid= 17224476 |doi=10.1161/CIRCULATIONAHA.106.668392}}</ref>
  | B3 ||{{OMIM2|114205}}||[[CACNA1C]]|| Alpha subunit of [[cardiac]] L-type [[calcium]] channel.<ref name="pmid 17224476">{{cite journal |author= Antzelevitch C, Pollevick GD, Cordeiro JM, et al  |title= Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death |journal=Circulation |volume=115 |issue=4 |pages=442–229 |year=2007 |pmid= 17224476 |doi=10.1161/CIRCULATIONAHA.106.668392}}</ref>
  |-  
  |-  
  | B4 || {{OMIM2|600003}} || [[CACNB2]] || Beta-2 subunit of the voltage dependent L-type calcium channel.<ref name="pmid 17224476">{{cite journal |author= Antzelevitch C, Pollevick GD, Cordeiro JM, et al  |title= Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death |journal=Circulation |volume=115 |issue=4 |pages=442–229 |year=2007 |pmid= 17224476 |doi=10.1161/CIRCULATIONAHA.106.668392}}</ref>
  | B4 ||{{OMIM2|600003}}||[[CACNB2]]|| Beta-2 subunit of the voltage dependent L-type [[calcium]] channel.<ref name="pmid 17224476">{{cite journal |author= Antzelevitch C, Pollevick GD, Cordeiro JM, et al  |title= Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death |journal=Circulation |volume=115 |issue=4 |pages=442–229 |year=2007 |pmid= 17224476 |doi=10.1161/CIRCULATIONAHA.106.668392}}</ref>


  |-  
  |-  
  | B5 || {{OMIM2|604433}} || [[KCNE3]] which coassembles with [[KCND3]] || Beta subunit to [[KCND3]]. Modulates the Ito potassium outward current<ref>{{cite journal|doi=10.1161/CIRCEP.107.748103|title=Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome|year=2008|author=Delpon E, Cordeiro JM, Núñez L, et al|journal=Circulation Arrhythmia and Electrophysiology |volume=1 |pages=209-18 |issue=3 |year=2008 |pmid=19122847 }}</ref>
  | B5 ||{{OMIM2|604433}}||[[KCNE3]] which coassembles with [[KCND3]]|| Beta subunit to [[KCND3]]. Modulates the Ito [[potassium]] outward current.<ref>{{cite journal|doi=10.1161/CIRCEP.107.748103|title=Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome|year=2008|author=Delpon E, Cordeiro JM, Núñez L, et al|journal=Circulation Arrhythmia and Electrophysiology |volume=1 |pages=209-18 |issue=3 |pmid=19122847 }}</ref>
  |-  
  |-  
  | B6 || {{OMIM2|600235}} || [[SCN1B]] || Beta-1 subunit of the sodium channel [[SCN5A]]<ref>{{cite journal|author=Watanabe H, Koopmann TT, Le Scouarnec S, ''et al'' |title=Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans |journal=J. Clin. Invest. |volume=118 |issue=6 |pages=2260–8 |year=2008 |month=June |pmid=18464934 |pmc=2373423 |doi=10.1172/JCI33891 |url=}}</ref>
  | B6 ||{{OMIM2|600235}}||[[SCN1B]]|| Beta-1 subunit of the [[sodium]] channel [[SCN5A]]<ref>{{cite journal|author=Watanabe H, Koopmann TT, Le Scouarnec S, ''et al'' |title=Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans |journal=J. Clin. Invest. |volume=118 |issue=6 |pages=2260–8 |year=2008 |month=June |pmid=18464934 |pmc=2373423 |doi=10.1172/JCI33891 |url=}}</ref>
|-
|-
  |}
  |}


Over 160 mutations in the SCN5A gene have been discovered to date, each having varying mechanisms and effects on function, thereby explaining the varying degrees of penetration and expression of this disorder. <ref name="pmid16972995">{{cite journal |author=Napolitano C, Priori SG |title=Brugada syndrome |journal=Orphanet journal of rare diseases |volume=1 |issue= |pages=35 |year=2006 |pmid=16972995 |doi=10.1186/1750-1172-1-35}}</ref>
* Over 160 [[Mutation|mutations]] in the [[SCN5A]] [[gene]] have been discovered to date, each having varying [[Mechanism (biology)|mechanisms]] and effects on function, thereby explaining the varying degrees of [[penetration]] and [[Gene expression|expression]] of this [[Disorder (medicine)|disorder]]. <ref name="pmid16972995">{{cite journal |author=Napolitano C, Priori SG |title=Brugada syndrome |journal=Orphanet journal of rare diseases |volume=1 |issue= |pages=35 |year=2006 |pmid=16972995 |doi=10.1186/1750-1172-1-35}}</ref>


An example of one of the mechanisms in which a loss of function of the sodium channel occurs is a mutation in the gene that disrupts the sodium channel's ability to bind properly to [[ankyrin]]-G, an important protein mediating interaction between ion channels and cytoskeletal elements. Very recently a mutation in a second gene, [[Glycerol-3-phosphate dehydrogenase]] 1-like gene ({{Gene|GPD1L}}) has been shown to result in Brugada Syndrome in a large multigenerational family (London, 2006). This gene acts as an ion channel modulator in the heart, although the exact mechanism is not yet understood.
* An example of one of the [[Mechanism of action|mechanisms]] in which a loss of function of the [[sodium]] channel occurs is a [[mutation]] in the [[gene]] that disrupts the [[sodium]] channel's ability to bind properly to [[ankyrin]]-G, an important [[protein]] mediating [[interaction]] between [[ion]] channels and [[cytoskeletal]] elements. Very recently a [[mutation]] in a second [[gene]], [[Glycerol-3-phosphate dehydrogenase]] 1-like [[gene]] ({{Gene|GPD1L}}) has been shown to result in Brugada Syndrome in a large multigenerational family (London, 2006). This [[gene]] acts as an ion channel modulator in the [[heart]], although the exact [[Mechanism (biology)|mechanism]] is not yet understood.


Recently Antzelevitch has identified mutations in the [[Voltage-dependent calcium channel|L-type calcium channel]] subunits ({{Gene|CACNA1C}} (A39V and G490R) and {{Gene|CACNB2}} (S481L)) leading to ST elevation and a relatively short QT interval (below 360 msec).<ref name="pmid17556198">{{cite journal |author=Antzelevitch C |title=Genetic basis of Brugada syndrome |journal=Heart rhythm : the official journal of the Heart Rhythm Society |volume=4 |issue=6 |pages=756–7 |year=2007 |pmid=17556198 |doi=10.1016/j.hrthm.2007.03.015}}</ref>
* Recently Antzelevitch has identified mutations in the [[Voltage-dependent calcium channel|L-type calcium channel]] subunits ({{Gene|CACNA1C}} (A39V and G490R) and {{Gene|CACNB2}} (S481L)) leading to ST elevation and a relatively short QT interval (below 360 msec).<ref name="pmid17556198">{{cite journal |author=Antzelevitch C |title=Genetic basis of Brugada syndrome |journal=Heart rhythm : the official journal of the Heart Rhythm Society |volume=4 |issue=6 |pages=756–7 |year=2007 |pmid=17556198 |doi=10.1016/j.hrthm.2007.03.015}}</ref>


This condition is inherited in an [[autosomal dominant]] pattern and is more common in males. In addition it has a higher prevalence in most Asian populations.<ref>Brugada Syndrome. Charles Antzelevitch, PH.D. PACE 2006; 29:1130–1159</ref> <ref>Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report. J Am Coll Cardiol 1992; 20:1391–1396.</ref> <ref>Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome. A decade of progress. Circ Res 2002; 91:1114–1119.</ref> <ref>Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Eur Heart J 2002; 23:1648–1654.</ref> <ref>Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Circulation 2002; 106:2514–2519.</ref> <ref>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; 111:659–670.</ref> <ref>Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome:Report of the second consensus conference. Heart Rhythm 2005; 2:429–440.</ref>
* This condition is inherited in an [[autosomal dominant]] pattern and is more common in [[Male|males]]. In addition it has a higher prevalence in most Asian populations.<ref>Brugada Syndrome. Charles Antzelevitch, PH.D. PACE 2006; 29:1130–1159</ref> <ref>Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report. J Am Coll Cardiol 1992; 20:1391–1396.</ref> <ref>Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome. A decade of progress. Circ Res 2002; 91:1114–1119.</ref> <ref>Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Eur Heart J 2002; 23:1648–1654.</ref> <ref>Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Circulation 2002; 106:2514–2519.</ref> <ref>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; 111:659–670.</ref> <ref>Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome:Report of the second consensus conference. Heart Rhythm 2005; 2:429–440.</ref>


===Genes===
# SCN5A is a gene that [[Encoding (memory)|encodes]] the alpha [[sodium]] unit of the cardiac sodium channel.  [[Mutation|Mutations]] in SCN5A account for about 15-30% of Brugada syndrome cases.  A negative [[Genetics|genetic]] test for SCN5A does not exclude that SCN5A is causing the [[clinical]] syndrome because the [[genetic]] tests do not evaluate for [[Mutation|mutations]] in promotors, [[Cryptic splice site|cryptic splicing]] [[Mutation|mutations]], or gross rearrangements in the [[protein]] product.<ref name="JuangHorie2016">{{cite journal|last1=Juang|first1=Jyh-Ming Jimmy|last2=Horie|first2=Minoru|title=Genetics of Brugada syndrome|journal=Journal of Arrhythmia|volume=32|issue=5|year=2016|pages=418–425|issn=18804276|doi=10.1016/j.joa.2016.07.012}}</ref>
# Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction [[disease]] and low sensitivity to procainamide resulting from decreased [[sodium]] current. It has a relatively good [[prognosis]].
# CACNA1C (alpha subunit of L-type [[cardiac]] [[calcium]] channel) and CACNB2b (beta subunit of L-type [[cardiac]] [[calcium]] channel) is associated with a shortened QT interval and a combinatin Brugada/Short QT interval [[syndrome]].<ref name="ZhangChen2018">{{cite journal|last1=Zhang|first1=Qing|last2=Chen|first2=Junjie|last3=Qin|first3=Yao|last4=Wang|first4=Juejin|last5=Zhou|first5=Lei|title=Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia|journal=Channels|volume=12|issue=1|year=2018|pages=201–218|issn=1933-6950|doi=10.1080/19336950.2018.1499368}}</ref><ref name="ZhangChen20182">{{cite journal|last1=Zhang|first1=Qing|last2=Chen|first2=Junjie|last3=Qin|first3=Yao|last4=Wang|first4=Juejin|last5=Zhou|first5=Lei|title=Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia|journal=Channels|volume=12|issue=1|year=2018|pages=201–218|issn=1933-6950|doi=10.1080/19336950.2018.1499368}}</ref>


# SCN5A is a gene that encodes the alpha sodium unit of the cardiac sodium channel.  Mutations in SCN5A account for about 15-30% of Brugada syndrome cases.  A negative genetic test for SCN5A does not exclude that SCN5A is causing the clinical syndrome because the genetic tests do not evaluate for mutations in promotors, cryptic splicing mutations, or gross rearrangements in the protein product.
==References==
# Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction disease and low sensitivity to procainamide resulting from decreased Isodium current. It has a relatively good prognosis.
{{Reflist|2}}
# CACNA1C (alpha subunit of L-type cardiac calcium channel) and CACNB2b (beta subunit of L-type cardiac calcium channel) is associated with a shortened QT interval and a combinatin Brugada/Short QT interval syndrome.


==References==
{{reflist|2}}
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[[CME Category::Cardiology]]
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Overview

Approximately 20% of persons with Brugada syndrome have a mutation in the gene SCN5A. This gene encodes for the sodium ion channel. The mutation is inherited in an autosomal dominant pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.

Pathophysiology

Type OMIM Mutation Notes
B1 601144 alpha subunit of the sodium channel (SCN5A) Current through this channel is commonly referred to as INa. Gain of this channel leads to an unopposed Ito current (KCND2)
B2 611778 GPD1L, Glycerol-3-phosphate dehydrogenase like peptide
B3 114205 CACNA1C Alpha subunit of cardiac L-type calcium channel.[4]
B4 600003 CACNB2 Beta-2 subunit of the voltage dependent L-type calcium channel.[4]
B5 604433 KCNE3 which coassembles with KCND3 Beta subunit to KCND3. Modulates the Ito potassium outward current.[5]
B6 600235 SCN1B Beta-1 subunit of the sodium channel SCN5A[6]
  • Recently Antzelevitch has identified mutations in the L-type calcium channel subunits (CACNA1C (A39V and G490R) and CACNB2 (S481L)) leading to ST elevation and a relatively short QT interval (below 360 msec).[8]
  1. SCN5A is a gene that encodes the alpha sodium unit of the cardiac sodium channel. Mutations in SCN5A account for about 15-30% of Brugada syndrome cases. A negative genetic test for SCN5A does not exclude that SCN5A is causing the clinical syndrome because the genetic tests do not evaluate for mutations in promotors, cryptic splicing mutations, or gross rearrangements in the protein product.[16]
  2. Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction disease and low sensitivity to procainamide resulting from decreased sodium current. It has a relatively good prognosis.
  3. CACNA1C (alpha subunit of L-type cardiac calcium channel) and CACNB2b (beta subunit of L-type cardiac calcium channel) is associated with a shortened QT interval and a combinatin Brugada/Short QT interval syndrome.[17][18]

References

  1. ↑ Lehnart, Stephan E.; Ackerman, Michael J.; Benson, D. Woodrow; Brugada, Ramon; Clancy, Colleen E.; Donahue, J. Kevin; George, Alfred L.; Grant, Augustus O.; Groft, Stephen C.; January, Craig T.; Lathrop, David A.; Lederer, W. Jonathan; Makielski, Jonathan C.; Mohler, Peter J.; Moss, Arthur; Nerbonne, Jeanne M.; Olson, Timothy M.; Przywara, Dennis A.; Towbin, Jeffrey A.; Wang, Lan-Hsiang; Marks, Andrew R. (2007). "Inherited Arrhythmias". Circulation. 116 (20): 2325–2345. doi:10.1161/CIRCULATIONAHA.107.711689. ISSN 0009-7322.
  2. ↑ Delpón, Eva; Cordeiro, Jonathan M.; Núñez, Lucía; Thomsen, Poul Erik Bloch; Guerchicoff, Alejandra; Pollevick, Guido D.; Wu, Yuesheng; Kanters, J�rgen K.; Larsen, Carsten Toftager; Hofman-Bang, Jacob; Burashnikov, Elena; Christiansen, Michael; Antzelevitch, Charles (2008). "Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome". Circulation: Arrhythmia and Electrophysiology. 1 (3): 209–218. doi:10.1161/CIRCEP.107.748103. ISSN 1941-3149. replacement character in |first8= at position 2 (help); line feed character in |title= at position 22 (help)
  3. ↑ Bueno-Orovio, Alfonso; Cherry, Elizabeth M.; Evans, Steven J.; Fenton, Flavio H. (2015). "Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome". BioMed Research International. 2015: 1–12. doi:10.1155/2015/197586. ISSN 2314-6133.
  4. ↑ 4.0 4.1 Antzelevitch C, Pollevick GD, Cordeiro JM; et al. (2007). "Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death". Circulation. 115 (4): 442–229. doi:10.1161/CIRCULATIONAHA.106.668392. PMID 17224476.
  5. ↑ Delpon E, Cordeiro JM, Núñez L; et al. (2008). "Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome". Circulation Arrhythmia and Electrophysiology. 1 (3): 209–18. doi:10.1161/CIRCEP.107.748103. PMID 19122847.
  6. ↑ Watanabe H, Koopmann TT, Le Scouarnec S; et al. (2008). "Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans". J. Clin. Invest. 118 (6): 2260–8. doi:10.1172/JCI33891. PMC 2373423. PMID 18464934. Unknown parameter |month= ignored (help)
  7. ↑ Napolitano C, Priori SG (2006). "Brugada syndrome". Orphanet journal of rare diseases. 1: 35. doi:10.1186/1750-1172-1-35. PMID 16972995.
  8. ↑ Antzelevitch C (2007). "Genetic basis of Brugada syndrome". Heart rhythm : the official journal of the Heart Rhythm Society. 4 (6): 756–7. doi:10.1016/j.hrthm.2007.03.015. PMID 17556198.
  9. ↑ Brugada Syndrome. Charles Antzelevitch, PH.D. PACE 2006; 29:1130–1159
  10. ↑ Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report. J Am Coll Cardiol 1992; 20:1391–1396.
  11. ↑ Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome. A decade of progress. Circ Res 2002; 91:1114–1119.
  12. ↑ Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Eur Heart J 2002; 23:1648–1654.
  13. ↑ Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Circulation 2002; 106:2514–2519.
  14. ↑ 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; 111:659–670.
  15. ↑ Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome:Report of the second consensus conference. Heart Rhythm 2005; 2:429–440.
  16. ↑ Juang, Jyh-Ming Jimmy; Horie, Minoru (2016). "Genetics of Brugada syndrome". Journal of Arrhythmia. 32 (5): 418–425. doi:10.1016/j.joa.2016.07.012. ISSN 1880-4276.
  17. ↑ Zhang, Qing; Chen, Junjie; Qin, Yao; Wang, Juejin; Zhou, Lei (2018). "Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia". Channels. 12 (1): 201–218. doi:10.1080/19336950.2018.1499368. ISSN 1933-6950.
  18. ↑ Zhang, Qing; Chen, Junjie; Qin, Yao; Wang, Juejin; Zhou, Lei (2018). "Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia". Channels. 12 (1): 201–218. doi:10.1080/19336950.2018.1499368. ISSN 1933-6950.

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