Department of Anesthesia and Pain Management, Toronto General Hospital, University of Toronto, ON, Canada.
Can J Anaesth. 2010 Jul;57(7):689-93. doi: 10.1007/s12630-010-9314-4. Epub 2010 Apr 30.
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.
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.
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.
报告在一名恶性高热患者中，发现电压门控骨骼肌 L 型钙通道的 α-1 亚单位（Cav1.1）编码基因 CACNA1S 的一种新突变。
一位 34 岁的健康女性在腹腔镜供肾切除术期间接受七氟醚麻醉后出现暴发性恶性高热（MH）。第一个迹象是呼气末 CO2 增加。早期怀疑恶性高热，并成功实施了复苏措施，包括支持和特异性治疗。由于患者拒绝进行咖啡因氟烷收缩试验（CHCT）的开放性肌肉活检，因此仅进行了分子遗传学检测。对整个兰尼碱受体 1 转录本进行测序未发现任何 MH 致病突变。然而，在编码骨骼肌 L 型钙通道（Cav1.1）α-1 亚单位的 CACNA1S 基因中发现了一种新的纯合突变，p.Arg1086Ser。涉及与我们患者中相同 Arg1086 残基的 CACNA1S 突变，p.Arg1086His，先前已在三个独立的家族中与 MH 相关报道。
CACNA1S 基因的纯合 p.Arg1086Ser 突变，该基因编码电压门控骨骼肌 L 型钙通道的 α-1 亚单位，是一种与恶性高热相关的新突变。
