• Lucia Galli, Alfredo Orrico, Stefania Lorenzini, Stefano Censini, Michela Falciani, Antonello Covacci, Vincenzo Tegazzin, and Vincenzo Sorrentino.
• Molecular Medicine Section, Department of Neuroscience, University of Siena and Azienda Ospedaliera Universitaria Senese, Siena, Italy.
• Hum. Mutat. 2006 Aug 1;27(8):830.

AbstractMalignant hyperthermia (MH) is a dominantly inherited pharmacogenetic condition that manifests as a life-threatening hypermetabolic reaction when a susceptible individual is exposed to common volatile anesthetics and depolarizing muscle relaxants. Although MH appears to be genetically heterogeneous, RYR1 is the main candidate for MH susceptibility. However, since molecular analysis is generally limited to exons where mutations are more frequently detected, these are routinely found only in 30-50% of susceptible subjects. In this study the entire RYR1 coding region was analyzed in a cohort of 50 Italian MH susceptible (MHS) subjects. Thirty-one mutations, 16 of which were novel, were found in 43 individuals with a mutation detection rate of 86%, the highest reported for RYR1 in MH so far. These data provide clear evidence that mutations in the RYR1 gene are the predominant cause of MH.

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