An R1632C variant in the SCN5A gene causing Brugada syndrome

García‑Molina,Esperanza; Sabater‑Molina,María; Muñoz,Carmen; Ruiz‑Espejo,Francisco; Gimeno,Juan  R.

doi:10.3892/mmr.2016.5100

An R1632C variant in the SCN5A gene causing Brugada syndrome

Authors:
- Esperanza García‑Molina
- María Sabater‑Molina
- Carmen Muñoz
- Francisco Ruiz‑Espejo
- Juan R. Gimeno
View Affiliations

Affiliations: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, El Palmar, 30120 Murcia, Spain, Department of Cardiology, Virgen de la Arrixaca University Hospital, El Palmar, 30120 Murcia, Spain
Published online on: April 11, 2016 https://doi.org/10.3892/mmr.2016.5100
Pages: 4677-4680

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Brugada syndrome (BS) is an electrical disease, inherited in an autosomal dominant manner. BS is caused by mutations in up to 13 different genes. SCN5A is the gene most frequently mutated in BS, although this presents an incomplete penetrance. The present case study investigated the SCN5A gene in a family exhibiting BS. Direct sequencing of the SCN5A gene was performed to identify mutations and a familial investigation was performed. A novel variant was identified in the voltage‑sensing domain of the SCN5A protein. This familial investigation revealed one novel asymptomatic carrier in the family. Genetic investigations are useful to classify individuals who require more frequent clinical monitoring and to stratify the risk of developing the disease.

View Figures

View References

1	Brugada R, Campuzano O, Sarquella-Brugada G, Brugada J and Brugada P: Brugada syndrome. Methodist Debakey Cardiovasc J. 10:25–28. 2014. View Article : Google Scholar : PubMed/NCBI
2	Potet F, Mabo P, Le Coq G, Probst V, Schott JJ, Airaud F, Guihard G, Daubert JC, Escande D and Le Marec H: Novel brugada SCN5A mutation leading to ST segment elevation in the inferior or the right precordial leads. J Cardiovasc Electrophysiol. 14:200–203. 2003. View Article : Google Scholar : PubMed/NCBI
3	Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, et al: Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 392:293–296. 1998. View Article : Google Scholar : PubMed/NCBI
4	Antzelevitch C: Ion channels and ventricular arrhythmias: Cellular and ionic mechanisms underlying the Brugada syndrome. Curr Opin Cardiol. 14:274–279. 1999. View Article : Google Scholar : PubMed/NCBI
5	Antzelevitch C: Genetic basis of brugada syndrome. Heart Rhythm. 4:756–757. 2007. View Article : Google Scholar : PubMed/NCBI
6	Moric E, Herbert E, Trusz-Gluza M, Filipecki A, Mazurek U and Wilczok T: The implications of genetic mutations in the sodium channel gene (SCN5A). Europace. 5:325–334. 2003. View Article : Google Scholar
7	Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, et al: Natural history of Brugada syndrome: Insights for risk stratification and management. Circulation. 105:1342–1347. 2002. View Article : Google Scholar : PubMed/NCBI
8	Schulze-Bahr E, Eckardt L, Breithardt G, Seidl K, Wichter T, Wolpert C, Borggrefe M and Haverkamp W: Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: Different incidences in familial and sporadic disease. Hum Mutat. 21:651–652. 2003. View Article : Google Scholar
9	Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Brignole M, Giordano U, Giovannini T, Menozzi C, Bloise R, et al: Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation. 102:2509–2515. 2000. View Article : Google Scholar : PubMed/NCBI
10	Bai R, Napolitano C, Bloise R, Monteforte N and Priori SG: Yield of genetic screening in inherited cardiac channelopathies: How to prioritize access to genetic testing. Circ Arrhythm Electrophysiol. 2:6–15. 2009. View Article : Google Scholar : PubMed/NCBI
11	Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, et al: An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 7:33–46. 2010. View Article : Google Scholar : PubMed/NCBI
12	Campuzano O, Allegue C, Iglesias A and Brugada R: Genetic basis of Brugada syndrome. J Genet Syndr Gene Ther. 4:72013.
13	Delpón E, Cordeiro JM, Núñez L, Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Hofman-Bang J, et al: Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol. 1:209–218. 2008. View Article : Google Scholar
14	London B, Michalec M, Mehdi H, Zhu X, Kerchner L, Sanyal S, Viswanathan PC, Pfahnl AE, Shang LL, Madhusudanan M, et al: Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na⁺ current and causes inherited arrhythmias. Circulation. 116:2260–2268. 2007. View Article : Google Scholar : PubMed/NCBI
15	Watanabe H, Koopmann TT, Le Scouarnec S, Yang T, Ingram CR, Schott JJ, Demolombe S, Probst V, Anselme F, Escande D, et al: Sodium channel β₁ subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. 118:2260–2268. 2008.PubMed/NCBI
16	Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B, et al: 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. 115:442–449. 2007. View Article : Google Scholar : PubMed/NCBI
17	Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, Kornblit CA, Angelilli A, Villanueva F, McNamara DM and London B: Clinical and molecular heterogeneity in the Brugada syndrome: A novel gene locus on chromosome 3. Circulation. 105:707–713. 2002. View Article : Google Scholar : PubMed/NCBI
18	Hedley PL, Jørgensen P, Schlamowitz S, Moolman-Smook J, Kanters JK, Corfield VA and Christiansen M: The genetic basis of Brugada syndrome: A mutation update. Hum Mutat. 30:1256–1266. 2009. View Article : Google Scholar : PubMed/NCBI
19	Gui J, Wang T, Jones RPO, Trump D, Zimmer T and Lei M: Multiple loss-of-function mechanisms contribute to SCN5A-related familial Sick Sinus Syndrome. PLoS ONE. 5:e109852010. View Article : Google Scholar : PubMed/NCBI