No evidence of mutations in the CACNA1S gene in the UK malignant hyperthermia population

Background. Malignant hyperthermia (MH) is an inherited, potentiallyfatal, pharmocogenetic disorder triggered by certain anaestheticagents. In light of the reported genetic heterogeneity for thedisorder and the recent introduction of DNA testing guidelinesfor the trait, we have assessed the role of the CACNA1S genein MH susceptibility in UK patients. Linkage to this locus haspreviously been demonstrated in several European MH families. Methods and results. We screened 200 unrelated MH-susceptibleindividuals for known CACNA1S mutations. With the aim to characterizefurther novel mutations at this locus, functionally relevantregions of the gene were also sequenced in 10 unrelated individualsfrom families where the involvement of other MH susceptibilityloci was unlikely. No sequence variations were detected in anyof the patients investigated. Conclusions. Defects in CACNA1S are not a major cause of MHin the UK population. Diagnostic screening of this gene is unlikelyto be of value to UK MH patients in the near future. Br J Anaesth 2002; 88: 587–9