Details of Disease

General Information of Disease (ID: DISSGN0E)

• Disease Name: Brugada syndrome
• Synonyms: sudden unexpected nocturnal death syndrome; Bangungut; right bundle branch block, ST segment elevation, and sudden death syndrome; SUNDS; idiopathic ventricular fibrillation, Brugada type; Pokkuri death syndrome; sudden unexplained nocturnal death syndrome; dream disease; Brugada syndrome; Brugada type idiopathic ventricular fibrillation
• Definition: A genetically heterogeneous condition characterized by complete or incomplete right bundle branch block accompanied by ST elevation in leads V1-V3. There is a high incidence of ventricular arrhythmia that may result in sudden death.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISMT2VZ: Cardiogenetic disease
  DISLKUNL: Heart arrhythmia
  DISSGN0E: Brugada syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0015263
  MESH ID: D053840
  UMLS CUI: C1142166
  MedGen ID: 222975
  Orphanet ID: 130
  SNOMED CT ID: 418818005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FGF14	TTKJX1V	Limited	Biomarker	[1]
IDS	TTNY2AP	Limited	Biomarker	[2]
SCN10A	TT90XZ8	Limited	Unknown	[3]
SCN4A	TT84DRB	Limited	Genetic Variation	[4]
CACNA1C	TTZIFHC	Disputed	Biomarker	[5]
CACNA2D1	TTFK1JQ	Disputed	Autosomal dominant	[6]
CACNA2D1	TTFK1JQ	Disputed	Biomarker	[7]
HCN4	TTQP04A	Disputed	Genetic Variation	[8]
KCND3	TTPLQO0	Disputed	Genetic Variation	[9]
KCNH2	TTQ6VDM	Disputed	Genetic Variation	[10]
TRPM4	TTJ2HKA	Disputed	Autosomal dominant	[11]
TRPM4	TTJ2HKA	Disputed	Genetic Variation	[12]
SEMA3A	TTVKD3S	Supportive	Autosomal dominant	[13]
ABCC9	TTEF5MJ	Strong	Biomarker	[14]
KCNQ1	TT846HF	Strong	Genetic Variation	[10]
MYH7	TTNIMDP	Strong	Biomarker	[15]
SCN5A	TTZOVE0	Definitive	Autosomal dominant	[11]

This Disease Is Related to 4 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCC9	DT3JCE6	Limited	Autosomal dominant	[3]
CACNB2	DTBZWL4	Disputed	Biomarker	[16]
CACNA1C	DTAIV1Z	Supportive	Autosomal dominant	[17]
KCNH2	DTD0BMQ	Moderate	Autosomal dominant	[3]

This Disease Is Related to 43 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ABCC9	OTGAXLQN	Limited	Autosomal dominant	[3]
CAV3	OTWSFDB4	Limited	Autosomal dominant	[3]
DEPDC5	OTE70JLY	Limited	Autosomal dominant	[6]
DLG1	OTCRZYWT	Limited	Unknown	[3]
EGR3	OTGPJIRA	Limited	Biomarker	[18]
FGF11	OT6513W2	Limited	Biomarker	[1]
FGF12	OTBM9QIO	Limited	Biomarker	[1]
KCNAB2	OTH115IE	Limited	Genetic Variation	[19]
KCND2	OTIFUVV7	Limited	Biomarker	[20]
KCNE1	OTZNQUW9	Limited	Biomarker	[21]
KCNE2	OTUO214Y	Limited	Biomarker	[21]
KCNJ8	OTZ8G8FE	Limited	Unknown	[3]
KCNK1	OTBXPTKX	Limited	Altered Expression	[22]
LRRC10	OT9V0ZBY	Limited	Biomarker	[23]
NOS1AP	OTDFOBRU	Limited	Genetic Variation	[24]
PKP2	OTJOVF68	Limited	Autosomal dominant	[3]
RRAD	OTW2O4GD	Limited	Autosomal dominant	[6]
RYR2	OT0PF19E	Limited	Genetic Variation	[25]
SCN10A	OTPCGJAC	Limited	Unknown	[3]
SCN4B	OT3JSUWO	Limited	Genetic Variation	[26]
ANK2	OTWB4R1Y	Disputed	Autosomal dominant	[11]
CACNA2D1	OT5YLZIH	Disputed	Autosomal dominant	[6]
KCNE3	OTKWKR91	Disputed	Autosomal dominant	[11]
KCNE5	OTF4JYGZ	Disputed	Autosomal dominant	[11]
RANGRF	OTKQC813	Disputed	Autosomal dominant	[11]
SCN1B	OTGD78J3	Disputed	Biomarker	[27]
TRPM4	OT354X8E	Disputed	Autosomal dominant	[11]
CACNA1C	OT6KFNMS	Supportive	Autosomal dominant	[17]
SCN2B	OTFAHJ38	Supportive	Autosomal dominant	[28]
SCNN1A	OTE2KVZV	Supportive	Autosomal dominant	[13]
SEMA3A	OTQJSV7W	Supportive	Autosomal dominant	[13]
SLMAP	OTHW3DVC	Supportive	Autosomal dominant	[17]
CALM2	OTNYA92F	moderate	GermlineCausalMutation	[29]
KCNH2	OTZX881H	Moderate	Autosomal dominant	[3]
AKAP9	OT7Z2YRP	Strong	Biomarker	[30]
DSG2	OTJPB2TO	Strong	Biomarker	[15]
ELOA	OTOQTF5K	Strong	Biomarker	[31]
ELOB	OTZ3X84T	Strong	Biomarker	[31]
ELOC	OT0XHHWP	Strong	Biomarker	[31]
HGS	OTCYYCAC	Strong	Biomarker	[32]
SKP1	OT5BPAZ4	Strong	Biomarker	[31]
SRSF5	OTC5WP98	Strong	Biomarker	[32]
SCN5A	OTGYZWR6	Definitive	Autosomal dominant	[11]

References

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• [2] Near-miss SIDS due to Brugada syndrome.Arch Dis Child. 2005 May;90(5):528-9. doi: 10.1136/adc.2004.058115.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies.Eur J Hum Genet. 2016 Mar;24(3):400-7. doi: 10.1038/ejhg.2015.125. Epub 2015 Jun 3.
• [5] Brugada syndrome and calcium channel mutation in a patient with congenital deaf mutism.Indian Pacing Electrophysiol J. 2017 Jan-Feb;17(1):16-17. doi: 10.1016/j.ipej.2017.01.002. Epub 2017 Jan 9.
• [6] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [7] Functional characterization of CaV2 mutations associated with sudden cardiac death.J Biol Chem. 2015 Jan 30;290(5):2854-69. doi: 10.1074/jbc.M114.597930. Epub 2014 Dec 19.
• [8] HCN4 Gene Variations in Sudden Unexplained Nocturnal Death Syndrome in the Southern Han Chinese Population.J Forensic Sci. 2019 Jul;64(4):1112-1118. doi: 10.1111/1556-4029.13958. Epub 2018 Nov 19.
• [9] Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.Seizure. 2019 Mar;66:26-30. doi: 10.1016/j.seizure.2019.01.025. Epub 2019 Jan 28.
• [10] Genetic Variants on SCN5A, KCNQ1, and KCNH2 in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction in a Chinese Population.Cardiology. 2020;145(1):38-45. doi: 10.1159/000502833. Epub 2019 Nov 21.
• [11] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [12] Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome.Cardiology. 2017;137(4):256-260. doi: 10.1159/000471792. Epub 2017 May 12.
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• [14] Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern China.Mayo Clin Proc. 2016 Nov;91(11):1503-1514. doi: 10.1016/j.mayocp.2016.06.031. Epub 2016 Oct 1.
• [15] High-throughput genetic characterization of a cohort of Brugada syndrome patients.Hum Mol Genet. 2015 Oct 15;24(20):5828-35. doi: 10.1093/hmg/ddv302. Epub 2015 Jul 28.
• [16] Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay.Circulation. 2012 Jan 3;125(1):14-22. doi: 10.1161/CIRCULATIONAHA.111.054007. Epub 2011 Nov 16.
• [17] Brugada Syndrome. 2005 Mar 31 [updated 2022 Aug 25]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [18] Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder?.Forensic Sci Int. 2014 Mar;236:38-45. doi: 10.1016/j.forsciint.2013.12.033. Epub 2014 Jan 7.
• [19] Dysfunction of the Voltage-Gated K+ Channel 2 Subunit in a Familial Case of Brugada Syndrome.J Am Heart Assoc. 2016 Jun 10;5(6):e003122. doi: 10.1161/JAHA.115.003122.
• [20] Genomic organisation and chromosomal localisation of two members of the KCND ion channel family, KCND2 and KCND3.Hum Genet. 2000 Jun;106(6):614-9. doi: 10.1007/s004390000308.
• [21] Postmortem molecular analysis of KCNQ1, KCNH2, KCNE1 and KCNE2 genes in sudden unexplained nocturnal death syndrome in the Chinese Han population.Forensic Sci Int. 2013 Sep 10;231(1-3):82-7. doi: 10.1016/j.forsciint.2013.04.020. Epub 2013 May 15.
• [22] Transcriptional profiling of ion channel genes in Brugada syndrome and other right ventricular arrhythmogenic diseases.Eur Heart J. 2009 Feb;30(4):487-96. doi: 10.1093/eurheartj/ehn520. Epub 2008 Nov 23.
• [23] Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population.Int J Legal Med. 2017 May;131(3):621-628. doi: 10.1007/s00414-016-1516-z. Epub 2016 Dec 28.
• [24] Association of common variants in NOS1AP gene with sudden unexplained nocturnal death syndrome in the southern Chinese Han population.Int J Legal Med. 2014 Nov;128(6):933-8. doi: 10.1007/s00414-014-0973-5. Epub 2014 Feb 7.
• [25] Channelopathies That Lead to Sudden Cardiac Death: Clinical and Genetic Aspects.Heart Lung Circ. 2019 Jan;28(1):22-30. doi: 10.1016/j.hlc.2018.09.007. Epub 2018 Oct 4.
• [26] Contribution of Cardiac Sodium Channel -Subunit Variants to Brugada Syndrome.Circ J. 2015;79(10):2118-29. doi: 10.1253/circj.CJ-15-0164. Epub 2015 Jul 15.
• [27] Sudden unexpected death in GEFS+ families with sodium channel pathogenic variants.Epilepsy Res. 2019 Feb;150:66-69. doi: 10.1016/j.eplepsyres.2019.01.009. Epub 2019 Jan 14.
• [28] A missense mutation in the sodium channel 2 subunit reveals SCN2B as a new candidate gene for Brugada syndrome. Hum Mutat. 2013 Jul;34(7):961-6. doi: 10.1002/humu.22328. Epub 2013 Apr 29.
• [29] Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders.PLoS One. 2016 Apr 21;11(4):e0153851. doi: 10.1371/journal.pone.0153851. eCollection 2016.
• [30] Brugada syndrome & AKAP9: Reconciling clinical findings with diagnostic uncertainty.J Electrocardiol. 2019 Nov-Dec;57:119-121. doi: 10.1016/j.jelectrocard.2019.09.013. Epub 2019 Sep 7.
• [31] Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.J Cardiovasc Electrophysiol. 2018 Jul;29(7):998-1003. doi: 10.1111/jce.13496. Epub 2018 Apr 20.
• [32] Update of diagnosis and management of inherited cardiac arrhythmias.Circ J. 2013;77(12):2867-72. doi: 10.1253/circj.cj-13-1217. Epub 2013 Nov 7.