Genetic screening for malignant hyperthermia and comparison of clinical symptoms in Japan

KANZAKI Rieko

MORINO Hiroyuki

MUKAIDA Keiko

KUME Kodai

OHSAWA Ryosuke

NODA Yuko

OTSUKI Sachiko

MIYOSHI Hirotsugu

KONDO Takashi

NAKAMURA Ryuji

KAWAMOTO Masashi

KAWAKAMI Hideshi

TSUTSUMI Yasuo

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

Malignant hyperthermia (MH) is an anaesthetic complication that causes an abnormal hypermetabolic state. RYR1 encoding ryanodine receptors of the sarcoplasmic reticulum and CACNA1S encoding α subunits of dihydropyridine receptors are known to be associated with MH pathogenicity. We performed genetic screening using next-generation sequencing to evaluate the prevalence of genes associated with MH pathogenicity and clinical symptoms. This was a retrospective cohort study wherein next-generation sequencing data of 77 families diagnosed with MH predisposition by calcium-induced calcium release (CICR) tests from 1995 to 2019 was used to search for RYR1 and CACNA1S variants. Furthermore, the clinical symptoms and predisposition tests in participants with RYR1 and CACNA1S variants were compared. In the 77 families, 44.2%, 7.8%, and 48.1% individuals had RYR1, CACNA1S, and neither RYR1 nor CACNA1S variants, respectively. Clinically significant differences were found in the maximum body temperature, maximum elevated body temperature for 15 min, creatinine kinase level, and CICR rate between the RYR1 and CACNA1S groups. The prevalence of pathogenic CACNA1S variants appears to be prominent in Japan. The severity of clinical symptoms and the CICR rate were greater in individuals with RYR1 variants than in those with CACNA1S variants, likely due to more direct regulation of calcium levels by ryanodine receptors than by dihydropyridine receptors. Genetic analysis of MH in future studies may help identify other genes associated with MH, which will further clarify the relationship between genotypes and MH symptoms and contribute to safer anaesthesia practice.

Malignant hyperthermia

Next Generation Sequencing

RYR1

CACNA1S

英語

Hiroshima University Medical Press

Copyright (c) 2022 Hiroshima University Medical Press

[ISSN] 0018-2052

[ISSN] 2433-7668

[NCID] AA00664312

[DOI] 10.24811/hjms.71.1-2_31