© 1992 Oxford University Press
RESEARCH-ARTICLE |
The genomic structure of the human skeletal muscle sodium channel gene
Molecular Neurogenetics Laboratory, Massachusetts General Hospital and Harvard Medical School Charlestown, MA 02129, USA 1Departments of Molecular Genetics and Biochemistry, Human Genetics, and Pediatrics, University of Pittsburgh PA 15261, USA
*To whom correspondence should be addressed at: Molecular Neurogenetics Laboratory, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA
Received August 18, 1992; Revised August 18, 1992; Accepted August 18, 1992
Electrical excitability of neurons and muscle cells reflects the actions of a family of structurally related sodium channels. Mutations in the adult skeletal muscle sodium channel have been associated with the inherited neuromuscular disorders paramyotonia congenita (PMC) and hyperkalemic periodic paralysis (HPP). We have deciphered the entire genomic structure of the human skeletal muscle sodium channel gene and developed a restriction map of the locus. SCN4A consists of 24 exons spanning 35 kb of distance on chromosome 17q. We describe the sequence of all intron/exon boundaries, the presence of several polymorphisms in the coding sequence, and the locations within introns of two dinucleotide repeat polymorphisms. This is the first sodium channel for which the entire genomic structure has been resolved. The organization of the SCN4A exons relative to the proposed protein structure is presented and represents a foundation for functional and evolutionary comparisons of sodium channels. Knowledge of the exon structure and flanking intron sequences for SCN4A will permit a systematic search for mutations in PMC and HPP.
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