title: Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees.
abstract: Malignant hyperthermia (MH) is rarely associated with specific myopathies or musculoskeletal abnormalities. Three clinical investigations of MH associated with either non-specific myopathies or congenital disorders in three separate families are presented. Two of these cases also show evidence of exercise-induced rhabdomyolysis. In each case MH susceptibility was confirmed by in vitro contracture testing of quadriceps muscle. DNA sequence analysis of each kindred revealed the presence of a common novel mutation that results in an arginine401-cysteine substitution in the skeletal muscle ryanodine receptor gene (RYR1). Haplotype analysis using chromosome 19q markers indicated that the three families are likely to be unrelated, providing confirmation that the MH/central core disease region 1 of RYR1 is a mutation hot spot.
authors.affiliation: Department of Neuropathology, Royal Perth Hospital, Western Australia.
authors.forename: M
authors.initials: M
authors.lastname: Davis
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Dickson
authors.forename: H
authors.initials: H
authors.lastname: Horton
authors.forename: D
authors.initials: D
authors.lastname: James
authors.forename: N
authors.initials: N
authors.lastname: Laing
authors.forename: R
authors.initials: R
authors.lastname: Marston
authors.forename: M
authors.initials: M
authors.lastname: Norgate
authors.forename: D
authors.initials: D
authors.lastname: Perlman
authors.forename: N
authors.initials: N
authors.lastname: Pollock
authors.forename: K
authors.initials: K
authors.lastname: Stowell
mesh_terms: D000595:Amino Acid Sequence; D001315:Australia; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D015444:Exercise; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000150:complications / Q000235:genetics*; D020125:Mutation, Missense; D009520:New Zealand; D010375:Pedigree; D012206:Rhabdomyolysis / Q000150:complications / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel