Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1

Long QT syndrome (LQT) is a cardiac disorder causing syncope and sudden death from arrhythmias. LQT is characterized by prolongation of the QT interval on electrocardiogram, an indication of abnormal cardiac repolarization. Mutations in KVLQT1, HERG, SCN5A, and KCNE1, genes encoding cardiac ion channels, cause LQT. Here, we define the complete genomic structure of three LQT genes and use this information to identify disease-associated mutations. KVLQT1 is composed of 16 exons and encompasses approximately 400 kb. HERG consists of 16 exons and spans 55 kb. Three exons make up KCNE1. Each intron of these genes contains the invariant GT and AG at the donor and acceptor splice sites, respectively. Intron sequences were used to design primer pairs for the amplification of all exons. Familial and sporadic cases affected by mutations in KVLQT1, HERG, and KCNE1 can now be genetically screened to identify individuals at risk of developing this disorder. This work has clinical implications for presymptomatic diagnosis and therapy. (C) 1998 Academic Press.