DETECTION OF A NOVEL RYR1 MUTATION IN 4 MALIGNANT HYPERTHERMIA PEDIGREES

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anaesthetics and depolarizing muscle re laxants. To date, six mutations in the skeletal muscle ryanodine recep tor gene (RYR1) have been identified in malignant hyperthermia suscept ible (MHS) and central core disease (CCD) cases. Using SSCP analysis, we have screened the RYR1 gene in affected individuals for novel MHS m utations and have identified a G to A transition mutation which result s in the replacement of a conserved Gly at position 2433 with an Arg. The Gly2433Arg mutation was present in four of 104 unrelated MHS indiv iduals investigated and was not detected in a normal population sample . This mutation is adjacent to the previously identified Arg2434His mu tation reported in a CCD/MH family and indicates that there may be a s econd region in the RYR1 gene where MHS/CCD mutations cluster.