Related Experiment Videos
A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia
T H Fagerlund1, G Islander, E R Twetman
1Institute of Medical Genetics, University of Oslo, Norway.
Insights
Malignant hyperthermia susceptibility in Swedish families was investigated. The Arg614Cys mutation in the RYR1 gene was found in 7% of families, suggesting other causative mutations exist.
Area of Science:
- Genetics
- Anesthesiology
- Molecular Biology
Background:
- Malignant hyperthermia (MH) is a severe pharmacogenetic disorder of skeletal muscle.
- Susceptibility to MH is strongly linked to specific mutations in the RYR1 gene.
- Eight RYR1 gene mutations are currently identified as causative for MH susceptibility.
Purpose of the Study:
- To investigate the prevalence of three known RYR1 gene mutations in Swedish families with MH.
- To identify the genetic basis of MH susceptibility in the studied population.
Main Methods:
- Screening of 41 Swedish families with a history of MH.
- Genetic analysis for three specific RYR1 mutations: Arg163Cys, Ile403Met, and Arg614Cys.
- Detection of Arg614Cys mutation (the "pig mutation").
Main Results:
- The Arg614Cys mutation was identified in 3 out of 41 families (7%).
- No other screened mutations (Arg163Cys, Ile403Met) were detected.
- This suggests limited contribution of these specific mutations to MH susceptibility in this cohort.
Conclusions:
- The screened RYR1 mutations are not the primary cause of MH susceptibility in most Swedish families.
- Further research is needed to identify novel causative mutations for MH in the Swedish population.
- Genetic heterogeneity of MH susceptibility is highlighted.
Abstract:
Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.