title: Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.
abstract: Malignant 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.
authors.affiliation: Molecular Medicine Section, Department of Neuroscience, University of Siena and Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Galli
authors.forename: Alfredo
authors.initials: A
authors.lastname: Orrico
authors.forename: Stefania
authors.initials: S
authors.lastname: Lorenzini
authors.forename: Stefano
authors.initials: S
authors.lastname: Censini
authors.forename: Michela
authors.initials: M
authors.lastname: Falciani
authors.forename: Antonello
authors.initials: A
authors.lastname: Covacci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tegazzin
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sorrentino
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel