Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families.
Defects in the genes coding for the skeletal muscle ryanodine receptor (RYR1) and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) have been identified as causative for malignant hyperthermia (MH). Sixty-two MH susceptible individuals presenting to the same diagnostic centre had copy deoxyribonucleic acid, derived from muscle ribonucleic acid, sequenced to identify variants with the potential to be responsible for the MH phenotype in both RYR1 and CACNA1S. These genetic findings were combined with clinical episode details and in vitro contracture test results to improve our understanding of the Australian MH cohort. Twelve novel variants were identified in RYR1 and six in CACNA1S. Known RYR1 causative mutations were identified in six persons and novel variants in RYR1 and CACNA1S in a further 17 persons. Trends indicated higher mutation identification in those with more definitive clinical episodes and stronger in vitro contracture test responses.
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, Victoria.
R L
RL
Gillies
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, Victoria.
A R
AR
Bjorksten
Victorian Clinical Genetics Services, Parkville, Victoria.
D
D
Du Sart
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, Victoria.
B M
BM
Hockey
D001315:Australia; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008305:Malignant Hyperthermia / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017421:Sequence Analysis / Q000379:methods
C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel
malignant hyperthermia; ryanodine receptor calcium release channel