Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2

Nature. 1990 Feb 8;343(6258):562-4. doi: 10.1038/343562a0.


Malignant hyperthermia (MH) is an inherited human skeletal muscle disorder and is one of the main causes of death due to anaesthesia. The reported incidence of MH varies from 1 in 12,000 in children to 1 in 40,000 in adults. MH is triggered in susceptible people by all commonly used inhalational anaesthetics; it is characterized by a profoundly accelerated muscle metabolism, contractures, hyperthermia and tachycardia. Susceptibility to MH (MHS) is predicted by contracture tests on muscle tissue obtained by biopsy. An almost identical disorder known as porcine MH exists in pigs. The genetics of the porcine syndrome have been extensively studied; the locus controlling expression of porcine MH is genetically linked to the glucose phosphate isomerase locus (GPI). In man, GPI has been mapped to the q12-13.2 region of chromosome 19 (refs 10-12). We have now investigated genetic linkage in several extended Irish pedigrees in which MHS is segregating as an autosomal dominant trait. Here we show linkage between MHS and DNA markers from the GPI region of human chromosome 19 with a maximum log likelihood ratio (lod score) of 5.65 at the CYP2A locus. These results indicate that human and porcine MH are most probably due to mutations in homologous genes, and also provide a potentially accurate and noninvasive method of diagnosis for MHS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 19*
  • Female
  • Genetic Linkage
  • Halothane / pharmacology
  • Humans
  • Lod Score
  • Male
  • Malignant Hyperthermia / genetics*
  • Muscle Contraction / drug effects
  • Pedigree
  • Receptors, Cholinergic / genetics
  • Recombination, Genetic
  • Ryanodine Receptor Calcium Release Channel
  • Swine / genetics


  • Receptors, Cholinergic
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Halothane