The search for novel causative genes of malignant hyperthermia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16733
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Hiroshima University
• Principal Investigator: Noda Yuko 広島大学, 病院(医), 医科診療医 (00790065)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 悪性高熱症 / リアノジン受容体 / ジヒドロピリジン受容体 / 次世代シークエンサー / 遺伝子

Outline of Final Research Achievements

We analyzed gene variants of ryanodine receptor (RYR1) and dihydropyridine receptor (CACNA1S) in patients with malignant hyperthermia and family history of malignant hyperthermia.
We identified 16 known mutations in RYR1 and CACNA1S and 17 variants with a high possibility of a new causative mutation.We also performed functional analysis of variants with a high possibility of a new causative mutation and confirmed whether it was the causative mutation or not.
Samples with no mutation in RYR1 and CACNA1S were submitted to the exome sequence to try to find a new causative variants. By submitting a total of 16 samples, we were able to narrow down the candidates for the causative variants.

Free Research Field

麻酔蘇生学

Academic Significance and Societal Importance of the Research Achievements

悪性高熱症は主にリアノジン受容体(RYR1)の遺伝子変異が原因であると言われているが，発症した患者のうち実際にRYR1から遺伝子変異が確認されない症例も多い．これはRYR1以外に未知の遺伝子要因が存在していることを示唆しているが，その探索は遅々として進んでおらず，今回の研究は，悪性高熱症の新たな原因遺伝子を探索し，悪性高熱症の遺伝子診断の確立に少なからず寄与できた．