Abstract 181 Cardiology: Signaling Mechanisms and Cardiovascular Function Platform, Sunday, 5/2

Background: Brugada Syndrome, also known as idiopathic ventricular fibrillation with right bundle branch block and ST segment elevation in the right precordial leads (V1-V3), is a significant cause of sudden cardiac death in children and young, healthy adults. We recently identified mutations in the cardiac sodium channel gene SCN5A ( Nature, 1998) as responsible in two families and one sporadic case. It is not currently known if other ion channels are involved in this disorder. The goal of this study was to analyze a large number of children and adults with Brugada syndrome for new gene mutations in SCN5A and other ion channel genes.

Material/Methods: Probands from 15 families and 41 sporadic cases were identified and blood was obtained for lymphoblastoid cell lines and DNA. PCR primers were designed to amplify portions of SCN5A, as well as other known ion channel genes, including the long QT syndrome associated potassium channels KVLQT1, HERG, and KCNE1, amongst others. Single strand conformational polymorphism (SSCP) mutation analysis was performed on all probands and, when abnormal, family members were subsequently analyzed. DNA sequencing was performed on all abnormal conformers.

Results: Novel Mutations were identified in SCN5A in two families and three sporadic cases. Although no other ion channel gene was found to be mutated, genetic heterogeneity was identified. All mutations significantly altered the ion channel protein structure. Biophysical studies are ongoing.

Conclusions: Brugada Syndrome is a malignant arrhythmia caused by heterogeneous mutations in SCN5A. This ion channelopathy displays evidence of genetic heterogeneity and the other causes of this disease are being evaluated.