A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia

• Published in: Genomics (San Diego, Calif.) Vol. 11; no. 3; p. 751
• Main Authors: Gillard, E F, Otsu, K, Fujii, J, Khanna, V K, de Leon, S, Derdemezi, J, Britt, B A, Duff, C L, Worton, R G, MacLennan, D H
• Format: Journal Article
• Language: English
• Published: United States 01-11-1991
• Subjects: Adolescent; Amino Acid Sequence; Arginine - genetics; Base Sequence; Caffeine - pharmacology; Cloning, Molecular; Cysteine - genetics; European Continental Ancestry Group - genetics; Exons - genetics; Female; Halothane - pharmacology; Humans; Male; Malignant Hyperthermia - diagnosis; Malignant Hyperthermia - genetics; Molecular Sequence Data; Muscle Proteins - chemistry; Muscle Proteins - genetics; Mutation - genetics; Oligodeoxyribonucleotides - genetics; Polymerase Chain Reaction; Receptors, Cholinergic - chemistry; Receptors, Cholinergic - genetics; Restriction Mapping; Ryanodine Receptor Calcium Release Channel
• ISSN: 0888-7543
• DOI: 10.1016/0888-7543(91)90084-R

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.