Investigation of new causative genes for malignant hyperthermia

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17783
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hiroshima University
• Principal Investigator: Kanzaki Rieko 広島大学, 病院(医), 寄附講座助教 (70751402)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 悪性高熱症 / 遺伝子解析 / RYR1 / CACNA1S

Outline of Final Research Achievements

Eight patients and their families with a predisposition to MH from the CICR test and six MH patients and their families who did not perform CICR test but were likely to have a predisposition to malignant hyperthermia were genetically screened using a next-generation sequencer. We found known causative gene in two samples. Variants in RYR1 and CACNA1S, which may be pathogenic were found in three samples. We plan to analyze the functions of these three variants and investigate whether they are new causative genes.

Free Research Field

悪性高熱症

Academic Significance and Societal Importance of the Research Achievements

今回の研究でRYR1およびCACNA1Sの中に病的である可能性の高いvariants(多様体)を3種類認めた。現段階では一般集団での該当遺伝子の存在する割合やbioinformaticsを用いた予測などからの推定なのでMHの原因遺伝子と完全に断定はできないが、今後機能解析を行うことで原因遺伝子だと確定する可能性は高い。筋生検を行わず低侵襲な血液からの遺伝子解析のみでMH素因を診断できる割合は、現在2割前後(当院にあるサンプルを参考にした場合)と低いが、今後、原因遺伝子と確定された遺伝子を少しずつ増やして行くことで、遺伝子解析でMH素因を診断できる割合を高くしていくことができる。