Steinfath M, Scholz J, Singh S, Wappler F
Abteilung für Anästhesiologie, Universitäts-Krankenhaus Eppendorf.
Anasthesiol Intensivmed Notfallmed Schmerzther. 1996 Aug;31(6):334-43. doi: 10.1055/s-2007-995932.
Malignant hyperthermia (MH) is a potentially fatal, inherited pharmacogenetic disorder characterised by a dysfunction of the intracellular calcium regulation. Linkage to DNA markers from the chromosome 19q12-13.2 region and the MHS-phenotype (MH susceptible) has been shown in about 50% of families with a history of MH. The ryanodine receptor gene encoding the human skeletal muscle ryanodine receptor has been localised to the chromosome 19q13.1-13.2 region. The ryanodine receptor, which is an intracellular calcium release channel, has been proposed to be one of the candidate structures for the MH defect. At present, eight different single point mutations have been identified in the human skeletal muscle ryanodine receptor gene in families with disposition to MH. The incidence of the various mutations has been reported as 2-10% each. A combination of different mutations within one pedigree has not been demonstrated. A few years ago, linkage of the MHS-phenotype to DNA markers from the chromosome 17q11.2-24 region was published by an American group. However, this observation has not been confirmed in any of the several European families susceptible to MH. Genes encoding for subunits of the dihydropyridine receptor and the sodium channel of the human skeletal muscle have been found to be located in the chromosome 17q11.2-24 region which, in fact, could be additional candidates for the MH defect. The dihydropyridine receptor is linked to the ryanodine receptor and involved in the calcium regulation of skeletal muscle. Very recent studies have shown linkage to DNA markers from chromosome 7q- and chromosome 3q13.1 regions and the MHS phenotype in two distinct families with history of MH. However, the relevance of this observation is so far unknown. At present, unambiguous preoperative screening of MH disposition based on molecular genetic characteristics is not available because of the enormous heterogeneity of the human MH syndrome. Thus, the halothane-caffeine in-vitro contracture test according to the standard protocol of the "European MH Group" must be performed in order to discover MH susceptibility.
恶性高热（MH）是一种潜在致命的遗传性药物遗传学疾病，其特征为细胞内钙调节功能障碍。在约50%有MH病史的家族中，已显示与19号染色体q12 - 13.2区域的DNA标记及MHS表型（MH易感性）存在连锁关系。编码人类骨骼肌兰尼碱受体的兰尼碱受体基因已定位至19号染色体q13.1 - 13.2区域。兰尼碱受体作为一种细胞内钙释放通道，被认为是MH缺陷的候选结构之一。目前，在有MH倾向的家族中，已在人类骨骼肌兰尼碱受体基因中鉴定出8种不同的单点突变。据报道，各种突变的发生率均为2% - 10%。尚未证实一个家系中存在不同突变的组合情况。几年前，一个美国研究小组发表了MHS表型与17号染色体q11.2 - 24区域的DNA标记的连锁关系。然而，在几个易患MH的欧洲家族中，这一观察结果均未得到证实。已发现编码人类骨骼肌二氢吡啶受体亚基和钠通道的基因位于17号染色体q11.2 - 24区域，实际上，它们可能是MH缺陷的其他候选基因。二氢吡啶受体与兰尼碱受体相连，并参与骨骼肌的钙调节。最近的研究表明，在两个有MH病史的不同家族中，7号染色体q - 和3号染色体q13.1区域的DNA标记与MHS表型存在连锁关系。然而，目前尚不清楚这一观察结果的相关性。目前，由于人类MH综合征存在巨大的异质性，基于分子遗传特征进行明确的术前MH倾向筛查尚不可行。因此，必须按照“欧洲MH小组”的标准方案进行氟烷 - 咖啡因体外挛缩试验，以发现MH易感性。
