GENOMIC ORGANIZATION OF THE HUMAN SCN5A GENE ENCODING THE CARDIAC SODIUM-CHANNEL

The voltage-gated cardiac sodium channel, SCN5A, is responsible for th e initial upstroke of the action potential. Mutations in the human SCN 5A gene cause susceptibility to cardiac arrhythmias and sudden death i n the long QT syndrome (LQT). In this report we characterize the genom ic structure of SCN5A. SCN5A consists of 28 exons spanning approximate ly 80 kb on chromosome 3p21. We describe the sequences of all intron/e xon boundaries and a dinucleotide repeat polymorphism in intron 16. Ol igonucleotide primers based on exon-flanking sequences amplify all SCN 5A exons by PCR. This work establishes the complete genomic organizati on of SCN5A and will enable high-resolution analyses of this locus for mutations associated with LQT and other phenotypes for which SCN5A ma y be a candidate gene. (C) 1996 Academic Press, Inc.