Identification of a mutation in the gene causing hyperkalemic periodic paralysis

Louis J. Ptáček, Alfred L. George, Robert C. Griggs, Rabi Tawil, Roland G. Kallen, Robert L. Barchi, Margaret Robertson, Mark F. Leppert

Research output: Contribution to journalArticlepeer-review

360 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1021-1027
Number of pages7
JournalCell
Volume67
Issue number5
DOIs
StatePublished - Nov 29 1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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