title: Identification of a mutation in the gene causing hyperkalemic periodic paralysis.
abstract: DNA from seven unrelated patients with hyperkalemic periodic paralysis (HYPP) was examined for mutations in the adult skeletal muscle sodium channel gene (SCN4A) known to be genetically linked to the disorder. Single-strand conformation polymorphism analysis revealed aberrant bands that were unique to three of these seven patients. All three had prominent fixed muscle weakness, while the remaining four did not. Sequencing the aberrant bands demonstrated the same C to T transition in all three unrelated patients, predicting substitution of a highly conserved threonine residue with a methionine in a membrane-spanning segment of this sodium channel protein. The observation of a distinct mutation that cosegregates with HYPP in two families and appears as a de novo mutation in a third establishes SCN4A as the HYPP gene. Furthermore, this mutation is associated with a form of HYPP in which fixed muscle weakness is seen.
authors.affiliation: Department of Neurology, Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt Lake City 84132.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ptácek
authors.forename: A L
authors.initials: AL
authors.lastname: George
authors.forename: R C
authors.initials: RC
authors.lastname: Griggs
authors.forename: R
authors.initials: R
authors.lastname: Tawil
authors.forename: R G
authors.initials: RG
authors.lastname: Kallen
authors.forename: R L
authors.initials: RL
authors.lastname: Barchi
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: M F
authors.initials: MF
authors.lastname: Leppert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005796:Genes; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics* / Q000473:pathology; D008961:Models, Structural; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels