title: Detection of a novel mutation in the ryanodine receptor gene in an Irish malignant hyperthermia pedigree: correlation of the IVCT response with the affected and unaffected haplotypes.
abstract: Defects in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia (MH), an autosomal dominant disorder of skeletal muscle and one of the main causes of death resulting from anaesthesia. Susceptibility to MH (MHS) is determined by the level of tension generated in an in vitro muscle contracture test (IVCT) in response to caffeine and halothane. To date, mutation screening of the RYR1 gene in MH families has led to the identification of eight mutations. We describe here the identification of a novel mutation, Arg552Trp, in the RYR1 gene, which is clearly linked to the MHS phenotype in a large, well characterised Irish pedigree. Considering that the RYR1 protein functions as a tetramer, correlation of the IVCT with the affected and unaffected haplotypes was performed on the pedigree to investigate if the normal RYR1 allele in affected subjects contributes to the variation in the IVCT. The results show that the normal RYR1 allele is unlikely to play a role in IVCT variation.
authors.affiliation: Department of Biochemistry, University College, Lee Maltings, Cork, Ireland.
authors.forename: K E
authors.initials: KE
authors.lastname: Keating
authors.forename: L
authors.initials: L
authors.lastname: Giblin
authors.forename: P J
authors.initials: PJ
authors.lastname: Lynch
authors.forename: K A
authors.initials: KA
authors.lastname: Quane
authors.forename: M
authors.initials: M
authors.lastname: Lehane
authors.forename: J J
authors.initials: JJ
authors.lastname: Heffron
authors.forename: T V
authors.initials: TV
authors.lastname: McCarthy
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000235:genetics*; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D019837:Ryanodine Receptor Calcium Release Channel
chemical_list: D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel