A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia

K. Hogan, Fergus J Couch, P. A. Powers, R. G. Gregg

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

A point mutation in the human gene for the skeletal muscle calcium release channel (ryanodine receptor [RYR1]) correlates with inheritance of malignant hyperthermia in a family of Northern European descent. The substitution of thymine for cytosine at position 1840 of the RYR1 transcript results in a cysteine-for-arginine substitution at position 614 (R614C) of the amino acid sequence. The mutation was absent in 59 normal individuals from the general population, in 61 additional unrelated malignant hyperthermia-susceptible patients, and in 18 patients with malignant hyperthermia associated with other inherited or congenital diseases. Together with reports of an equivalent mutation in six susceptible pig strains and an identical mutation in one other human pedigree, these findings suggest that the cysteine for-arginine mutation represents a shared calcium release channel pathogenesis between porcine malignant hyperthermia and a subset of mutations responsible for the human malignant hyperthermia syndrome.

Original languageEnglish (US)
Pages (from-to)441-448
Number of pages8
JournalAnesthesia and Analgesia
Volume75
Issue number3
StatePublished - 1992
Externally publishedYes

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Malignant Hyperthermia
Calcium Channels
Cysteine
Arginine
Skeletal Muscle
Mutation
Swine
Ryanodine Receptor Calcium Release Channel
Thymine
Cytosine
Pedigree
Point Mutation
Amino Acid Sequence
Population
Genes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia. / Hogan, K.; Couch, Fergus J; Powers, P. A.; Gregg, R. G.

In: Anesthesia and Analgesia, Vol. 75, No. 3, 1992, p. 441-448.

Research output: Contribution to journalArticle

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