title: Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.
abstract: 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.
authors.affiliation: Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown.
authors.forename: A I
authors.initials: AI
authors.lastname: McClatchey
authors.forename: P
authors.initials: P
authors.lastname: Van den Bergh
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: W
authors.initials: W
authors.lastname: Raskind
authors.forename: C
authors.initials: C
authors.lastname: Verellen
authors.forename: D
authors.initials: D
authors.lastname: McKenna-Yasek
authors.forename: K
authors.initials: K
authors.lastname: Rao
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: T
authors.initials: T
authors.lastname: Bird
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003080:Cold Temperature; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; D015222:Sodium Channels