Phenotypic Characterization of a Large European Family with Brugada Syndrome Displaying a Sudden Unexpected Death Syndrome Mutation in SCN5A

Female Predominance in the Signs and Symptoms of the Disease

Kui Hong, Antonio Berruezo-Sanchez, Naravat Poungvarin, Antonio Oliva, Matteo Vatta, Josep Brugada, Pedro Brugada, Jeffrey Towbin, Robert Dumaine, Carlos Piñero-Galvez, Charles Antzelevitch, Ramon Brugada

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Introduction: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V1 to V3 of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. Methods and Results: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. Conclusion: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome.

Original languageEnglish (US)
Pages (from-to)64-69
Number of pages6
JournalJournal of cardiovascular electrophysiology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Brugada Syndrome
Sudden Death
Signs and Symptoms
Ajmaline
Mutation
Electrocardiography
Cardiac Arrhythmias
Sodium Channel Blockers
Missense Mutation
Haplotypes
Phenotype

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Phenotypic Characterization of a Large European Family with Brugada Syndrome Displaying a Sudden Unexpected Death Syndrome Mutation in SCN5A : Female Predominance in the Signs and Symptoms of the Disease. / Hong, Kui; Berruezo-Sanchez, Antonio; Poungvarin, Naravat; Oliva, Antonio; Vatta, Matteo; Brugada, Josep; Brugada, Pedro; Towbin, Jeffrey; Dumaine, Robert; Piñero-Galvez, Carlos; Antzelevitch, Charles; Brugada, Ramon.

In: Journal of cardiovascular electrophysiology, Vol. 15, No. 1, 01.01.2004, p. 64-69.

Research output: Contribution to journalArticle

Hong, Kui ; Berruezo-Sanchez, Antonio ; Poungvarin, Naravat ; Oliva, Antonio ; Vatta, Matteo ; Brugada, Josep ; Brugada, Pedro ; Towbin, Jeffrey ; Dumaine, Robert ; Piñero-Galvez, Carlos ; Antzelevitch, Charles ; Brugada, Ramon. / Phenotypic Characterization of a Large European Family with Brugada Syndrome Displaying a Sudden Unexpected Death Syndrome Mutation in SCN5A : Female Predominance in the Signs and Symptoms of the Disease. In: Journal of cardiovascular electrophysiology. 2004 ; Vol. 15, No. 1. pp. 64-69.
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T2 - Female Predominance in the Signs and Symptoms of the Disease

AU - Hong, Kui

AU - Berruezo-Sanchez, Antonio

AU - Poungvarin, Naravat

AU - Oliva, Antonio

AU - Vatta, Matteo

AU - Brugada, Josep

AU - Brugada, Pedro

AU - Towbin, Jeffrey

AU - Dumaine, Robert

AU - Piñero-Galvez, Carlos

AU - Antzelevitch, Charles

AU - Brugada, Ramon

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Y1 - 2004/1/1

N2 - Introduction: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V1 to V3 of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. Methods and Results: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. Conclusion: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome.

AB - Introduction: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V1 to V3 of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. Methods and Results: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. Conclusion: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome.

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