Dihydropyridine receptor mutations cause hypokalemic periodic paralysis

Louis J. Ptáček, Rabi Tawil, Robert C. Griggs, Andrew G. Engel, Robert B. Layzer, Hubert Kwieciński, Philip G. McManis, Lorna Santiago, Mary Moore, Gameil Fouad, Paige Bradley, Mark F. Leppert

Research output: Contribution to journalArticle

346 Scopus citations

Abstract

Hypokalemic periodic paralysis (hypoKPP) is an autosomal dominant skeletal muscle disorder manifested by episodic weakness associated with low serum potassium. Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine (DHP) receptor gene. This receptor functions as a voltage-gated calcium channel and is also critical for excitation-contraction coupling in a voltage-sensitive and calcium-independent manner. We have characterized patient-specific DHP receptor mutations in 11 probands of 33 independent hypoKPP kindreds that occur at one of two adjacent nucleotides within the same codon and predict substitution of a highly conserved arginine in the S4 segment of domain 4 with either histidine or glycine. In one kindred, the mutation arose de novo. Taken together, these data establish this DHP receptor as the hypoKPP gene. We are unaware of any other human diseases presently known to result from DHP receptor mutations.

Original languageEnglish (US)
Pages (from-to)863-868
Number of pages6
JournalCell
Volume77
Issue number6
DOIs
StatePublished - Jun 17 1994

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Dihydropyridine receptor mutations cause hypokalemic periodic paralysis'. Together they form a unique fingerprint.

  • Cite this

    Ptáček, L. J., Tawil, R., Griggs, R. C., Engel, A. G., Layzer, R. B., Kwieciński, H., McManis, P. G., Santiago, L., Moore, M., Fouad, G., Bradley, P., & Leppert, M. F. (1994). Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell, 77(6), 863-868. https://doi.org/10.1016/0092-8674(94)90135-X