Albert Grievink

Citation

Thesis Title
Malignant hyperthermia: Allele specific expression and mutation screening of the ryanodine receptor 1

Mr. Grievink studied malignant hyperthermia, a skeletal muscle disorder caused by mutations in the ryanodine receptor that can cause a fatal hypermetabolic reaction to general anaesthetics. Allele-specific differences in ryanodine receptor expression levels can provide insight into the observed variations in malignant hyperthermia phenotypes between individuals. Therefore, an allele-specific polymerase chain reaction (PCR) assay was designed that allowed for the quantification of the two ryanodine receptor transcripts in heterozygous samples. In all samples allelic imbalances were detected, with the wild type allele being expressed at higher levels than the mutant allele. In an additional study, assays were developed that allowed screening for ryanodine receptor mutations associated with both malignant hyperthermia and central core disease. The identification of these mutations can eliminate the need for an invasive skeletal muscle biopsy for diagnosis of susceptibility to malignant hyperthermia

Supervisors
Professor Kathryn Stowell
Associate Professor Max Scott