Identification of Gene Variants Related to Malignant Hyperthermia in Han Chinese People by Next-Generation Sequencing.

Abstract

Background: Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by anesthesia. In recent years, next generation sequencing(NGS) technology, targeted sequencing approaches have been used to identify regions related to MH and can not only detect known MH variant sites but also allow the exploration of novel MH-related variants.Methods: Twenty-four volunteer’s blood samples were collected, genomic DNA was then extracted, target regions were amplified, and through targeted sequencing of these target regions, both known and novel variants were identified, and analysis of these variants identified some that may damage protein function. Online prediction tools were also used to determine the possibility of variants that may cause MH.Results: We performed next-generation sequencing of 53 positions on 4 genes, in which 36 variants of the RYR1 gene were found. Three of these caused a change in the amino acid sequence. Additionally, 11 variants of the CACNA1S gene were found, of which 3 led to amino acid sequence changes. Five variants of the JSRP1 gene were found, and four variants caused the amino acid sequence to change.Conclusions: In healthy volunteers, variants in RYR1 and CACNA1S were more common, and variants in JSRP1 more commonly had amino acid sequence changes. Whether a variant is pathogenic can be predicted using a prediction website, but the sensitivity and specificity still need to be improved.