Gillies R L, Bjorksten A R, Du Sart D, Hockey B M
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, Victoria.
Victorian Clinical Genetics Services, Parkville, Victoria.
Anaesth Intensive Care. 2015 Mar;43(2):157-66. doi: 10.1177/0310057X1504300204.
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.
编码骨骼肌兰尼碱受体（RYR1）和二氢吡啶受体α1亚基（CACNA1S）的基因缺陷已被确定为恶性高热（MH）的病因。62名到同一诊断中心就诊的MH易感个体接受了从肌肉核糖核酸衍生而来的拷贝脱氧核糖核酸测序，以确定RYR1和CACNA1S中可能导致MH表型的变异。这些基因研究结果与临床发作细节和体外挛缩试验结果相结合，以增进我们对澳大利亚MH队列的了解。在RYR1中鉴定出12个新变异，在CACNA1S中鉴定出6个新变异。在6人身上鉴定出已知的RYR1致病突变，在另外17人身上鉴定出RYR1和CACNA1S的新变异。趋势表明，在临床发作更明确、体外挛缩试验反应更强的个体中，突变鉴定率更高。
