Malignant hyperthermia susceptibility, an autosomal dominant disorder?
A large series of Swedish nuclear families, in which malignant hyperthermia (MH) reactions had occurred during anaesthesia, have been examined with respect to malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of muscle strips were conducted to diagnose MH status. Included in this series were some families where only one of the parents was tested by IVCT, while in 79 of the families both parents were tested by IVCT. Six known mutations in the gene encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear families. The present paper focuses on findings in eight families, where both parents were malignant hyperthemia negative (MHN), while at least one child was either malignant hyperthermia susceptible (MHS) or malignant hyperthermia equivocal (MHE). There was no suggestion of non-paternity. The RYR1 mutations investigated were Arg163Cys, Gly341Arg, Ile403Met, Arg614Cys, Gly2433Arg and Arg2434His. No family had any of the six RYR1 mutations searched for.
Fagerlund
T H
TH
Institute of Medical Genetics, University of Oslo, Norway.
Islander
G
G
Ranklev Twetman
E
E
Berg
K
K
D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects; D009154:Mutation; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D006221:Halothane