title: Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores.
abstract: The ryanodine receptor gene (RYR1) has been shown to be mutated in a small number of malignant hyperthermia (MH) pedigrees. Missense mutations in this gene have also been identified in two families with central core disease (CCD), a rare myopathy closely associated with MH. In an effort to identify other RYR1 mutations responsible for MH and CCD, we used a SSCP approach to screen the RYR1 gene for mutations in a family exhibiting susceptibility to MH (MHS) where some of the MHS individuals display core regions in their muscle. Sequence analysis of a unique aberrant SSCP has allowed us to identify a point mutation cosegregating with MHS in the described family. The mutation changes a conserved tyrosine residue at position 522 to a serine residue. This mutation is positioned relatively close to five of the six MHS/CCD mutations known to date and provides further evidence that MHS/CCD mutations may cluster in the amino terminal region of the RYR1 protein.
authors: Department of Biochemistry, University College, Cork, Ireland.
authors: K A
authors: KA
authors: Quane
authors: K E
authors: KE
authors: Keating
authors: J M
authors: JM
authors: Healy
authors: B M
authors: BM
authors: Manning
authors: R
authors: R
authors: Krivosic-Horber
authors: I
authors: I
authors: Krivosic
authors: N
authors: N
authors: Monnier
authors: J
authors: J
authors: Lunardi
authors: T V
authors: TV
authors: McCarthy
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D019837:Ryanodine Receptor Calcium Release Channel; D012694:Serine; D014443:Tyrosine
chemical_list: D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014443:Tyrosine; D012694:Serine