Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores

Genomics. 1994 Sep 1;23(1):236-9. doi: 10.1006/geno.1994.1483.


The ryanodine receptor gene (RYR1) has been shown to be mutated in a small number of malignant hyperthermia (MH) pedigrees. Missense mutations in this gene have also been identified in two families with central core disease (CCD), a rare myopathy closely associated with MH. In an effort to identify other RYR1 mutations responsible for MH and CCD, we used a SSCP approach to screen the RYR1 gene for mutations in a family exhibiting susceptibility to MH (MHS) where some of the MHS individuals display core regions in their muscle. Sequence analysis of a unique aberrant SSCP has allowed us to identify a point mutation cosegregating with MHS in the described family. The mutation changes a conserved tyrosine residue at position 522 to a serine residue. This mutation is positioned relatively close to five of the six MHS/CCD mutations known to date and provides further evidence that MHS/CCD mutations may cluster in the amino terminal region of the RYR1 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium Channels / genetics*
  • Cardiomyopathy, Hypertrophic / genetics
  • Chromosomes, Human, Pair 19
  • DNA Mutational Analysis
  • Female
  • Genes
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Male
  • Malignant Hyperthermia / genetics*
  • Molecular Sequence Data
  • Muscle Proteins / genetics*
  • Myopathies, Nemaline / genetics*
  • Pedigree
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Ryanodine Receptor Calcium Release Channel
  • Serine
  • Tyrosine


  • Calcium Channels
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Tyrosine
  • Serine