Novel mutations in domain I of SCN5A cause Brugada syndrome

Matteo Vatta, Robert Dumaine, Charles Antzelevitch, Ramon Brugada, Hua Li, Neil E. Bowles, Koonlawee Nademanee, Josep Brugada, Pedro Brugada, Jeffrey Towbin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Brugada syndrome, an autosomal dominantly inherited form of ventricular fibrillation characterized by ST-segment elevation in leads V1-V3 and right bundle-branch block on surface electrocardiogram, is caused by mutations in the cardiac sodium channel gene SCN5A. Patients with Brugada syndrome were studied using single-strand conformation polymorphism analysis, denaturing high-performance liquid chromatography, and DNA sequencing of SCN5A. Mutations were identified in SCN5A in two families and one sporadic case. In one family, a missense mutation leading to a glycine to valine sustitution (G351V) in the pore region between the DIS5 and DIS6 transmembrane segments was detected. Biophysical analysis demonstrated that this mutation caused significant current reduction. In the other family, a 20-bp deletion of the exon 5 splice acceptor site was identified; as exon 5 encodes part of the intracellular loop between DIS2 and DIS3, this portion of the channel is disrupted. In the sporadic patient, a missense mutation resulting in the substitution of lysine by glutamic acid (K126E) in the intracellular loop at the boundary with DIS1 was identified. These three new SCN5A mutations in Brugada syndrome patients are all located within domain I of SCN5A, a region not previously considered important in the development of ventricular arrhythmias.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalMolecular Genetics and Metabolism
Volume75
Issue number4
DOIs
StatePublished - Sep 12 2002

Fingerprint

Brugada Syndrome
Exons
RNA Splice Sites
Mutation
Sodium Channels
Valine
High performance liquid chromatography
Missense Mutation
Polymorphism
Electrocardiography
Glycine
Lysine
Conformations
Glutamic Acid
Substitution reactions
Genes
Bundle-Branch Block
DNA
Ventricular Fibrillation
DNA Sequence Analysis

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Vatta, M., Dumaine, R., Antzelevitch, C., Brugada, R., Li, H., Bowles, N. E., ... Towbin, J. (2002). Novel mutations in domain I of SCN5A cause Brugada syndrome. Molecular Genetics and Metabolism, 75(4), 317-324. https://doi.org/10.1016/S1096-7192(02)00006-9

Novel mutations in domain I of SCN5A cause Brugada syndrome. / Vatta, Matteo; Dumaine, Robert; Antzelevitch, Charles; Brugada, Ramon; Li, Hua; Bowles, Neil E.; Nademanee, Koonlawee; Brugada, Josep; Brugada, Pedro; Towbin, Jeffrey.

In: Molecular Genetics and Metabolism, Vol. 75, No. 4, 12.09.2002, p. 317-324.

Research output: Contribution to journalArticle

Vatta, M, Dumaine, R, Antzelevitch, C, Brugada, R, Li, H, Bowles, NE, Nademanee, K, Brugada, J, Brugada, P & Towbin, J 2002, 'Novel mutations in domain I of SCN5A cause Brugada syndrome', Molecular Genetics and Metabolism, vol. 75, no. 4, pp. 317-324. https://doi.org/10.1016/S1096-7192(02)00006-9
Vatta M, Dumaine R, Antzelevitch C, Brugada R, Li H, Bowles NE et al. Novel mutations in domain I of SCN5A cause Brugada syndrome. Molecular Genetics and Metabolism. 2002 Sep 12;75(4):317-324. https://doi.org/10.1016/S1096-7192(02)00006-9
Vatta, Matteo ; Dumaine, Robert ; Antzelevitch, Charles ; Brugada, Ramon ; Li, Hua ; Bowles, Neil E. ; Nademanee, Koonlawee ; Brugada, Josep ; Brugada, Pedro ; Towbin, Jeffrey. / Novel mutations in domain I of SCN5A cause Brugada syndrome. In: Molecular Genetics and Metabolism. 2002 ; Vol. 75, No. 4. pp. 317-324.
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