Identification of A Novel Mutation in RYR1 Gene in Malignant Hyperthermia-Like Patient's Family Members

Malignant hyperthermia (MH) is a rare pharmacogenetic disorder with an autosomal dominant inheritance that presents as a hypermetabolic response in skeletal muscle to volatile anaesthetic (halothane, isoflurane, desflurane, sevoflurane) and the depolarising muscle relaxant succinil-choline and rarely to stresses such as vigorous exercise and heat. We investigated the relatives of an individual with suspected MH and found a novel mutation in RYR1 gene. The molecular analysis of RYR1 gene revealed a novel nucleotide substitution in exon 6 - G528T (Glu-176-Asp) in four family members of the patient. The in vitro contracture test (IVCT) according to the European Malignant Hyperthermia Group (EMHG) guidelines showed a MH susceptible phenotype in two tested family members.