Identification of A Novel Mutation in Ryrl 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 succinilcholine 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.