title: A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia.
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.
authors.affiliation: Department of Anesthesiology, University of Wisconsin, Madison 53692.
authors.forename: K
authors.initials: K
authors.lastname: Hogan
authors.forename: F
authors.initials: F
authors.lastname: Couch
authors.forename: P A
authors.initials: PA
authors.lastname: Powers
authors.forename: R G
authors.initials: RG
authors.lastname: Gregg
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D003545:Cysteine / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D011950:Receptors, Cholinergic / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel; D013552:Swine
chemical_list: D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D004247:DNA; D001120:Arginine; D003545:Cysteine