Vita G M, Olckers A, Jedlicka A E, George A L, Heiman-Patterson T, Rosenberg H, Fletcher J E, Levitt R C
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Anesthesiology. 1995 May;82(5):1097-103. doi: 10.1097/00000542-199505000-00002.
Succinylcholine-induced masseter muscle rigidity (MMR) is a potentially life-threatening complication of anesthesia and is closely correlated with the heterogeneous disorder malignant hyperthermia (MH) susceptibility. MMR also is identified with a variety of neuromuscular disorders, including the myotonias, that are associated with abnormal in vitro contracture test (IVCT) results. Recently, mutations in the adult skeletal muscle sodium channel alpha-subunit gene (SCN4A) have been shown to cause generalized nondystrophic myotonias, some of which are associated with mild nonspecific symptoms. The purpose of the current investigation was to begin to evaluate the molecular genetic relationship between known mutations in the SCN4A gene, MMR, and the results of the IVCT used to diagnose MH-susceptibility.
A single extended pedigree of 16 individuals was ascertained through a proband who experienced MMR and whole-body rigidity after succinylcholine administration. Subsequently, four individuals were shown to have a mild form of myotonia on clinical and laboratory examination. IVCT was carried out according to standardized protocols. Mutations in the SCN4A gene were sought in exons 22 and 24 using single-strand conformational analyses. Variability in the SCN4A gene sequence was confirmed by direct DNA sequence analyses.
Four individuals with myotonia were shown to carry a guanine-to-cytosine mutation at nucleotide position 3917 of the reported SCN4A sequence. This DNA mutation was coinherited with MMR and an abnormal IVCT result in this family. Previous studies have demonstrated that the glycine1306-to-alanine substitution is associated with a mild clinical syndrome referred to as myotonia fluctuans.
The current report provides direct evidence that succinylcholine-induced MMR, whole-body rigidity, and an abnormal IVCT result are associated with a mutation in the SCN4A gene.
琥珀酰胆碱诱导的咬肌痉挛（MMR）是一种潜在的危及生命的麻醉并发症，与异质性疾病恶性高热（MH）易感性密切相关。MMR也与多种神经肌肉疾病相关，包括肌强直，这些疾病与体外挛缩试验（IVCT）结果异常有关。最近，成人骨骼肌钠通道α亚基基因（SCN4A）的突变已被证明可导致全身性非营养不良性肌强直，其中一些与轻度非特异性症状有关。本研究的目的是开始评估SCN4A基因已知突变、MMR和用于诊断MH易感性的IVCT结果之间的分子遗传关系。
通过一名在给予琥珀酰胆碱后出现MMR和全身僵硬的先证者确定了一个由16人组成的单一扩展家系。随后，通过临床和实验室检查发现4人有轻度肌强直形式。根据标准化方案进行IVCT。使用单链构象分析在第22和24外显子中寻找SCN4A基因的突变。通过直接DNA序列分析确认SCN4A基因序列的变异性。
4名患有肌强直的个体在报告的SCN4A序列的核苷酸位置3917处携带鸟嘌呤到胞嘧啶的突变。该DNA突变与该家族中的MMR和异常IVCT结果共同遗传。先前的研究表明，甘氨酸1306到丙氨酸的替代与一种称为波动性肌强直的轻度临床综合征有关。
本报告提供了直接证据，表明琥珀酰胆碱诱导的MMR、全身僵硬和异常IVCT结果与SCN4A基因的突变有关。
