The role of the skeletal muscle ryanodine receptor gene in malignant hyperthermia.

摘要: Malignant hyperthermia (MH) is an inherited, potentially lethal condition in which sustained muscle contracture with attendant hypermetabolism and triggered humans, heterozygous for the gene defect, by inhalational anaesthetics skeletal relaxants, pigs, homozygous stress. Because could result from a defective Ca2+ release channel, we have focussed our attention on linkage of MH to defects (RYR1) encoding channel. We cloned sequenced human RYR1 cDNA found restriction fragment length polymorphisms (RFLPs) gene. also localized chromosome 19q13.1. Studies cosegregation these RFLPs established RYR1/MH 19q13.1 (lod score 4.2; recombinant fraction 0.0). then normal porcine cDNAs. Mutation C1843 T, leading substitution Cys Arg615, was sole amino acid change noted between animals. Linkage this mutation study 338 informative meioses 102; identified corresponding 1 35 families studied MH. The combination high lod crossing species barrier supports causal nature mutation. Future studies are aimed at finding major mutations establishing assays their accurate diagnosis.