Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

Journal Article (Journal Article)

Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder.

Full Text

Duke Authors

Cited Authors

  • McClatchey, AI; Van den Bergh, P; Pericak-Vance, MA; Raskind, W; Verellen, C; McKenna-Yasek, D; Rao, K; Haines, JL; Bird, T; Brown, RH

Published Date

  • February 21, 1992

Published In

Volume / Issue

  • 68 / 4

Start / End Page

  • 769 - 774

PubMed ID

  • 1310898

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/0092-8674(92)90151-2


  • eng

Conference Location

  • United States