No evidence of mutations in the CACNA1S gene in the UK malignant hyperthermia population.
BACKGROUND
Malignant hyperthermia (MH) is an inherited, potentially fatal, pharmocogenetic disorder triggered by certain anaesthetic agents. In light of the reported genetic heterogeneity for the disorder and the recent introduction of DNA testing guidelines for the trait, we have assessed the role of the CACNA1S gene in MH susceptibility in UK patients. Linkage to this locus has previously been demonstrated in several European MH families.


RESULTS
We screened 200 unrelated MH-susceptible individuals for known CACNA1S mutations. With the aim to characterize further novel mutations at this locus, functionally relevant regions of the gene were also sequenced in 10 unrelated individuals from families where the involvement of other MH susceptibility loci was unlikely. No sequence variations were detected in any of the patients investigated.


CONCLUSIONS
Defects in CACNA1S are not a major cause of MH in the UK population. Diagnostic screening of this gene is unlikely to be of value to UK MH patients in the near future.
Brooks
C
C
MH Investigation Unit, St James' University Hospital, Leeds, UK.
Robinson
R L
RL
Halsall
P J
PJ
Hopkins
P M
PM
D020746:Calcium Channels, L-Type / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008305:Malignant Hyperthermia / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
D020746:Calcium Channels, L-Type