Genetics and pathogenesis of malignant hyperthermia

Citation
K. Jurkat-rott et al., Genetics and pathogenesis of malignant hyperthermia, MUSCLE NERV, 23(1), 2000, pp. 4-17
Citations number
173
Categorie Soggetti
da verificare
Journal title
MUSCLE & NERVE
ISSN journal
0148639X → ACNP
Volume
23
Issue
1
Year of publication
2000
Pages
4 - 17
Database
ISI
SICI code
0148-639X(200001)23:1<4:GAPOMH>2.0.ZU;2-E
Abstract
Malignant hyperthermia (MH) is a potentially life-threatening event in resp onse to anesthetic triggering agents, with symptoms of sustained uncontroll ed skeletal muscle calcium homeostasis resulting in organ and systemic fail ure. Susceptibility to MH, an autosomal dominant trait, may be associated w ith congenital myopathies, but in the majority of the cases, no clinical si gns of disease are visible outside of anesthesia. For diagnosis, a function al test on skeletal muscle biopsy, the in vitro contracture test (IVCT), is performed. Over 50% of the families show linkage of the IVCT phenotype to the gene encoding the skeletal muscle ryanodine receptor and over 20 mutati ons therein have been described. At least five other loci have been defined implicating greater genetic heterogeneity than previously assumed, but so far only one further gene encoding the main subunit of the voltage-gated di hydropyridine receptor has a confirmed role in NIH. As a result of extensiv e research on the mechanisms of excitation-contraction coupling and recent functional characterization of several disease-causing mutations in heterol ogous expression systems, much is known today about the molecular etiology of MH, (C) 2000 John Wiley & Sons, Inc.