Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia.
Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia.
复制标题
转诊诊断恶性高热的患者中兰尼碱受体突变的基因型和表型关系。
DOI：
10.1093/bja/75.3.307
复制
发表时间：
1995
影响因子：
9.8
通讯作者：
Rosenberg,H
中科院分区：
文献类型：
--
作者：
Fletcher,JE;Tripolitis,L;Hubert,M;Vita,GM;Levitt,RC;Rosenberg,H
麻醉引起的恶性高热（MH）可能是由骨骼肌兰尼碱受体的特定基因缺陷引起的。我们研究了 C1840T 突变（类似于猪突变）以及与 MH 和中央核心疾病相关的三种突变（G7301A、C487T 和 C1209G）的发生频率。根据北美 MH 组方案，我们调查了 137 名 MH 易感性测试呈阴性的患者和 101 名测试呈阳性的患者的骨骼肌标本。通过聚合酶链式反应和限制酶消化来确定突变的存在或不存在。在 MH 阳性受试者中，C1840T 和 C487T 突变的发生频率分别为 2% 和 1%，并且是唯一确定的两种突变。一名患有中央核心疾病的受试者没有检测到与该疾病相关的三种突变中的任何一种。因此，在兰尼定受体中检查的猪和中央核心疾病相关突变仅占 MH 阳性诊断的一小部分（约 3%）。检查的突变并未发生在任何 MH 阴性患者中，这支持了兰尼定受体缺陷与 MH 阳性诊断之间的关联。（摘要截断为 250 字）
Anaesthesia-induced malignant hyperthermia (MH) may be caused by specific gene defects in the skeletal muscle ryanodine receptor. We have studied the frequency of occurrence of the C1840T mutation, analogous to the porcine mutation, and three mutations associated both with MH and central core disease (G7301A, C487T and C1209G). We investigated skeletal muscle specimens from up to 137 patients testing negative and 101 patients testing positive for MH susceptibility by the North American MH Group protocol. The presence or absence of the mutations was determined by polymerase chain reaction and restriction enzyme digestion. The frequencies of occurrence of the C1840T and C487T mutations were 2% and 1%, respectively, in MH-positive subjects and were the only two mutations identified. One subject with central core disease did not have any of the three mutations examined associated with this disorder. Therefore, the porcine and central core disease-associated mutations examined in the ryanodine receptor account for a small proportion (approximately 3%) of MH-positive diagnoses. The mutations examined did not occur in any of the MH-negative patients, supporting an association between defects in the ryanodine receptor and a positive diagnosis for MH.(ABSTRACT TRUNCATED AT 250 WORDS)