A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.
Malignant hyperthermia (MH) is a devastating, potentially lethal response to anesthetics that occurs in genetically predisposed individuals. The skeletal muscle ryanodine receptor (RYR1) gene has been linked to porcine and human MH. Furthermore, a Cys for Arg substitution tightly linked to, and potentially causative of, porcine MH has been identified in the ryanodine receptor. Analysis of 35 human families predisposed to malignant hyperthermia has revealed the presence, and cosegregation with phenotype, of the corresponding substitution in a single family. This substitution, by analogy to the findings in pig, may be causal for predisposition to MH in this family.
Gillard
E F
EF
Department of Genetics, Hospital for Sick Children, Ontario, Canada.
Otsu
K
K
Fujii
J
J
Khanna
V K
VK
de Leon
S
S
Derdemezi
J
J
Britt
B A
BA
Duff
C L
CL
Worton
R G
RG
MacLennan
D H
DH
D000293:Adolescent; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D002110:Caffeine / Q000494:pharmacology; D003001:Cloning, Molecular; D003545:Cysteine / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics*; D015183:Restriction Mapping; D019837:Ryanodine Receptor Calcium Release Channel; D044465:White People / Q000235:genetics
D009124:Muscle Proteins; D009838:Oligodeoxyribonucleotides; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D001120:Arginine; D003545:Cysteine; D006221:Halothane