MALIGNANT HYPERTHERMIA - A LARGE KINDRED LINKED TO THE RYR1 GENE

Malignant hyperthermia susceptibility is genetically heterogeneous. Th e ryanodine receptor gene on the long arm of chromosome 19 represents an important candidate gene bur not all families with malignant hypert hermia demonstrate ryanodine receptor mutations or linkage to this leg ion of 19q. Linkage to chromosome 17 in the region of the adult muscle sodium channel alpha subunit gene has been suggested in some families ; others are nor linked to either of these loci. For most families the in vitro muscle contracture test remains the only reliable method of predicting susceptibility to malignant hyperthermia. We have performed linkage analysis in a large family group with malignant hyperthermia in which the in vitro muscle contracture test had been carried out usi ng the procedure standardised by the European Malignant Hyperthermia G roup. None of the published ryanodine receptor gene mutations associat ed with malignant hyperthermia susceptibility were detected in affecte d individuals but linkage to intragenic ryanodine receptor markers str ongly suggest that this gene is involved in malignant hyperthermia sus ceptibility in this family. This enabled accurate predictive testing b y DNA analysis in 11 untested subjects at 50% risk.