CARDIAC SODIUM-CHANNEL MUTATIONS IN PATIENTS WITH LONG QT SYNDROME, AN INHERITED CARDIAC-ARRHYTHMIA

Long QT syndrome (LQT) is an inherited cardiac disorder that causes sy ncope, seizures and sudden death from ventricular tachyarrhythmias. We used single-strand conformation polymorphism (SSCP) and DNA sequence analyses to identify mutations in the cardiac sodium channel gene, SCN 5A, in affected members of four LQT families. These mutations include two identical intragenic deletions and two missense mutations. These d ata suggest that SCN5A mutations cause LQT. The location and character of these mutations suggest that this form of LQT results from a delay in cardiac sodium channel fast inactivation or altered voltage-depend ence of inactivation.