DETECTION OF A NOVEL MUTATION AT AMINO-ACID POSITION-614 IN THE RYANODINE RECEPTOR IN MALIGNANT HYPERTHERMIA

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscul ar blocking agents. To date, eight mutations in the skeletal muscle ry anodine receptor gene (RYR1) have been identified in malignant hyperth ermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and ha ve identified a G to T transition mutation which results in the replac ement of a conserved arginine (Arg) at position 614 with a leucine (Le u). The Arg614Leu mutation was present in three unrelated MHS individu als of 151 investigated. The mutation was not detected in 148 normal c hromosomes and segregated precisely with MHS in family members from on e of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mu tation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cy s probands is presented.