title: Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.
abstract: Hyperkalemic periodic paralysis (hyperKPP) and paramyotonia congenita (PC) are genetic muscle disorders sharing the common features of myotonia and episodic weakness. In hyperKPP, patient symptoms and signs are worsened by elevated serum potassium, whereas in PC, muscle cooling exacerbates the condition. There are patients in whom features of both hyperKPP and PC are present. These diseases result from molecular alterations in the adult skeletal muscle sodium channel. This report summarizes our sodium channel mutation analysis in 25 families with hyperKPP and PC. We also report the putative disease-causing mutation in acetazolamide-responsive myotonia congenita, a related disease in which myotonia is worsened by potassium but in which episodic weakness does not occur. This missense mutation (I1160V) occurs at a very highly conserved position in the sodium channel, cosegregates with the disease, and was not present in any of a large panel of normal DNAs. Electrophysiologic characterization of specific mutations will lead to better understanding of the biophysics of this voltage-gated ion channel.
authors.affiliation: Department of Neurology, University of Utah Health Sciences Center, Salt Lake City 84132.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ptáĉek
authors.forename: R
authors.initials: R
authors.lastname: Tawil
authors.forename: R C
authors.initials: RC
authors.lastname: Griggs
authors.forename: G
authors.initials: G
authors.lastname: Meola
authors.forename: P
authors.initials: P
authors.lastname: McManis
authors.forename: R J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: J R
authors.initials: JR
authors.lastname: Mendell
authors.forename: C
authors.initials: C
authors.lastname: Harris
authors.forename: R
authors.initials: R
authors.lastname: Spitzer
authors.forename: F
authors.initials: F
authors.lastname: Santiago
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use*; D001345:Autoradiography; D001483:Base Sequence; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009224:Myotonia Congenita / Q000188:drug therapy / Q000235:genetics*; D009690:Nucleic Acid Conformation; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels; D000086:Acetazolamide