Variants in ASPH cause exertional heat illness and are associated with malignant hyperthermia susceptibility

Yukari Endo, Linda Groom, Alper Celik, Natalia Kraeva, Chang Seok Lee, Sung Yun Jung, Lois Gardner, Marie-Anne Shaw, Susan L. Hamilton, Philip M. Hopkins, Robert T. Dirksen, Sheila Riazi () and James J. Dowling ()
Additional contact information
Yukari Endo: Hospital for Sick Children
Linda Groom: University of Rochester
Alper Celik: Hospital for Sick Children
Natalia Kraeva: Malignant Hyperthermia Unit, Department of Anesthesia, Toronto General Hospital
Chang Seok Lee: Baylor College of Medicine
Sung Yun Jung: Baylor College of Medicine
Lois Gardner: University of Leeds
Marie-Anne Shaw: University of Leeds
Susan L. Hamilton: Baylor College of Medicine
Philip M. Hopkins: University of Leeds
Robert T. Dirksen: University of Rochester
Sheila Riazi: Malignant Hyperthermia Unit, Department of Anesthesia, Toronto General Hospital
James J. Dowling: Hospital for Sick Children

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling. We validated the pathogenicity of these variants using orthogonal pre-clinical models, CRISPR-edited C2C12 myotubes and transgenic zebrafish. In total, we demonstrate that ASPH variants represent a new cause of EHI and MH susceptibility.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31088-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31088-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31088-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().