Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita

Louis J. Ptáček, Alfred L. George, Robert L. Barchi, Robert C. Griggs, Jack E. Riggs, Margaret Robertson, Mark F. Leppert

Research output: Contribution to journalArticlepeer-review

238 Scopus citations

Abstract

The periodic paralyses are a group of autosomal dominant muscle diseases sharing a common feature of episodic paralysis. In one form, paramyotonia congenita (PC), the paralysis usually occurs with muscle cooling. Electrophysiologic studies of muscle from PC patients have revealed temperature-dependent alterations in sodium channel (NaCh) function. This observation led to demonstration of genetic linkage of a skeletal muscle NaCh gene to a PC disease allele. We now report the use of the single-strand conformation polymorphism technique to define alleles specific to PC patients from three families. Sequencing of these alleles defined base pair changes within the same codon, which resulted in two distinct amino acid substitutions for a highly conserved arginine residue in the S4 helix of domain 4 in the adult skeletal muscle NaCh. These data establish the chromosome 17q NaCh locus as the PC gene and represent two mutations causing the distinctive, temperature-sensitive PC phenotype.

Original languageEnglish (US)
Pages (from-to)891-897
Number of pages7
JournalNeuron
Volume8
Issue number5
DOIs
StatePublished - May 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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