A report of fulminant malignant hyperthermia in a patient with a novel mutation of the CACNA1S gene.
OBJECTIVE
To report the identification of a novel mutation in the CACNA1S gene that encodes the alpha-1-subunit (Cav1.1) of the voltage-gated skeletal muscle L-type calcium channel in a patient with malignant hyperthermia.


RESULTS
An otherwise healthy 34-yr-old female developed fulminant malignant hyperthermia (MH) under sevoflurane anesthesia during laparoscopic donor nephrectomy. The first sign was an increase in end-tidal CO(2). Malignant hyperthermia was suspected early, and resuscitative measures, including supportive and specific treatment, were successfully implemented. The patient rejected the open muscle biopsy for the Caffeine-Halothane Contracture Test (CHCT); therefore, only molecular genetic testing was performed. Sequencing of the entire ryanodine receptor type 1 transcript did not reveal any MH causative mutations. However, a novel homozygous mutation, p.Arg1086Ser, was identified in the CACNA1S gene that encoded for the alpha-1-subunit of the skeletal muscle L-type calcium channel (Cav1.1). A CACNA1S mutation, p.Arg1086His, involving the same Arg1086 residue that is mutated in our patient has previously been reported in association with MH in three independent families.


CONCLUSIONS
The homozygous p.Arg1086Ser mutation of CACNA1S, the gene that encodes the alpha-1-subunit of the voltage-gated skeletal muscle L-type calcium channel, is a novel mutation associated with malignant hyperthermia.
Toppin
P Jason
PJ
Department of Anesthesia and Pain Management, Toronto General Hospital, University of Toronto, ON, Canada.
Chandy
Tony T
TT
Ghanekar
Anand
A
Kraeva
Natalia
N
Beattie
W Scott
WS
Riazi
Sheila
S
D000328:Adult; D000758:Anesthesia; D001784:Blood Gas Analysis; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D004247:DNA / Q000235:genetics; D003620:Dantrolene / Q000627:therapeutic use; D004298:Dopamine / Q000627:therapeutic use; D004837:Epinephrine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D019520:Living Donors; D008305:Malignant Hyperthermia / Q000188:drug therapy / Q000235:genetics*; D016343:Monitoring, Intraoperative; D009125:Muscle Relaxants, Central / Q000627:therapeutic use; D009154:Mutation / Q000502:physiology; D011028:Pneumoperitoneum, Artificial; D012076:Renal Agents / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009125:Muscle Relaxants, Central; D012076:Renal Agents; D014662:Vasoconstrictor Agents; D004247:DNA; D003620:Dantrolene; D004298:Dopamine; D004837:Epinephrine