A case of discordance between genotype and phenotype in a malignant hyperthermia family

Eur J Hum Genet. 1999 May-Jun;7(4):415-20. doi: 10.1038/sj.ejhg.5200314.

Abstract

Malignant hyperthermia (MH) is an inherited autosomal dominant pharmacogenetic disorder and is the major cause of anaesthesia-induced death. Malignant hyperthermia susceptibility is usually diagnosed by the in vitro contracture test (IVCT) performed on fresh muscle biopsies exposed to caffeine and halothane, respectively. Around 50% of affected families are linked to the ryanodine receptor (RYR1) gene. The human RYR1 gene maps to chromosome 19q13.1 and encodes a protein that associates as a homotetramer and acts as a calcium-release channel from the sarcoplasmic reticulum. To date, 17 mutations have been identified in the coding region of the RYR1 gene and appear to be associated to the MH-susceptible phenotype. Here we describe a rare case of discordance between genotype (characterised by the presence of the Arg614Cys mutation in the RYR1 gene) and MH-normal typed phenotype. Although the IVCT remains a very reliable procedure for the assessment of MH status, genetic data can provide in some cases an additional aid to clinical diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caffeine
  • Chromosomes, Human, Pair 19
  • Disease Susceptibility
  • Family
  • Female
  • Genotype
  • Halothane
  • Humans
  • Male
  • Malignant Hyperthermia / genetics*
  • Malignant Hyperthermia / physiopathology*
  • Muscle Contraction / drug effects
  • Muscle, Skeletal / drug effects
  • Mutation
  • Pedigree
  • Phenotype
  • Ryanodine Receptor Calcium Release Channel / genetics*

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Halothane