Abstract
MALIGNANT hyperthermia (MH) is an inherited human skeletal muscle disorder and is one of the main causes of death due to anaesthesia1. The reported incidence of MH varies from 1 in 12,000 in children to 1 in 40,000 in adults2,3. MH is triggered in susceptible people by all commonly used inhalational anaesthetics; it is characterized by a profoundly accelerated muscle metabolism, contractures, hyperthermia and tachycardia1,4,5. Susceptibility to MH (MHS) is predicted by contracture tests on muscle tissue obtained by biopsy6,7. An almost identical disorder known as porcine MH exists in pigs8,9. The genetics of the porcine syndrome have been extensively studied10; the locus controlling expression of porcine MH is genetically linked to the glucose phosphate isomerase locus (GPI)11. 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Britt, B. A. in Malignant Hyperthermia (ed. Britt, B. A.) 325–367 (Martinus-Nijhoff, Amsterdam, 1987).
Britt, B. A. & Kalow, W. Can. Anaesth. Soc. J. 17, 293 (1970).
Snow, J. C. Archs Opthal., N.Y. 84, 407 (1970).
Berman, M. C., Harrison, G. G., Bull, A. B. & Kench, J. E. Nature 225, 653–655 (1970).
Ellis, F. R. & Heffron, J. J. A. in Recent Advances in Anaesthesia and Analgesia (eds Atkinson, R. S. & Adams, A. P.) 173–207 (Churchill-Livingstone, New York, 1985).
Rosenberg, H. & Reed, S. Anesth. Analg. 62, 415–420 (1983).
European Malignant Hyperpyrexia Group Br. J. Anaesth. 56, 1267–1271 (1984).
Hall, L. W., Woolf, N., Bradley, J. W. P. & Jolly, D. W. Br. med. J. 2, 1305 (1966).
Harrison, G. G. et al. Br. med. J. 3, 594–595 (1968).
Archibald, A. L. & Imlah, P. Anim. Blood Grps biochem. Genet. 16, 253–263 (1985).
Andresen, E. & Jensen, P. Nord. Vet. Med. 29, 502–504 (1977).
Ingram, P. H. et al. Biochem. Genet. 15, 455–476 (1977).
Brook, J. D. et al. Hum. Genet. 68, 282–285 (1984).
Lusis, A. J. et al. Proc. natn. Acad. Sci. U.S.A. 83, 3929–3933 (1986).
Ording, H. in Malignant Hyperthermia (ed. Britt, B. A.) 267–277 (Martinus-Nijhoff, Amsterdam 1987).
Eiberg, H. et al. Cytogenet Cell Genet. 51, 994 (1989).
Rasmusen, B. A. & Christian, L. L. Science 191, 947–948 (1976).
Schonk, D. et al. Genomics 4, 384–396 (1989).
Harley, H. et al. Cytogenet. Cell Genet. 51, 1011 (1989).
Nakamura, Y. et al. Genomics 3, 67–71 (1988).
Lathrop, G. M. et al. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).
Mickelson, J. R. et al. J. biol. Chem. 263, 9310–9315 (1988).
MacLennan, D. H. et al. Am. J. hum. Genet. Suppl. 45, abstract 803 (1989).
MacLennan, D. H. et al. Nature 343, 559–561 (1990).
Shaw, D. J. et al. Hum. Genet 83, 71–74 (1989).
Brunner, H. G. et al. Genomics 5, 589–595 (1989).
Johnson, K. et al. Genomics 5, 746–752 (1989).
Korneluk, R. G. et al. Genomics 5, 596–604 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McCarthy, T., Healy, J., Heffron, J. et al. Localization of the malignant hyperthermia susceptibility locus to human chromosome 19ql2–13.2. Nature 343, 562–564 (1990). https://doi.org/10.1038/343562a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/343562a0
This article is cited by
-
The 100 most cited articles in malignant hyperthermia
Anesthesiology and Perioperative Science (2023)
-
Inhalative Analgosedierung auf der Intensivstation
Medizinische Klinik - Intensivmedizin und Notfallmedizin (2020)
-
Genetics without genes? The centrality of genetic markers in livestock genetics and genomics
History and Philosophy of the Life Sciences (2019)
-
Telefonische Anfragen zum Thema maligne Hyperthermie
Der Anaesthesist (2016)
-
Pharmakogenetik in Anästhesie und Intensivmedizin
Der Anaesthesist (2016)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.