McCarthy T V, Healy J M, Heffron J J, Lehane M, Deufel T, Lehmann-Horn F, Farrall M, Johnson K
Department of Biochemistry, University College, Cork, Ireland.
Nature. 1990 Feb 8;343(6258):562-4. doi: 10.1038/343562a0.
Malignant hyperthermia (MH) is an inherited human skeletal muscle disorder and is one of the main causes of death due to anaesthesia. The reported incidence of MH varies from 1 in 12,000 in children to 1 in 40,000 in adults. MH is triggered in susceptible people by all commonly used inhalational anaesthetics; it is characterized by a profoundly accelerated muscle metabolism, contractures, hyperthermia and tachycardia. Susceptibility to MH (MHS) is predicted by contracture tests on muscle tissue obtained by biopsy. An almost identical disorder known as porcine MH exists in pigs. The genetics of the porcine syndrome have been extensively studied; the locus controlling expression of porcine MH is genetically linked to the glucose phosphate isomerase locus (GPI). In man, GPI has been mapped to the q12-13.2 region of chromosome 19 (refs 10-12). We have now investigated genetic linkage in several extended Irish pedigrees in which MHS is segregating as an autosomal dominant trait. Here we show linkage between MHS and DNA markers from the GPI region of human chromosome 19 with a maximum log likelihood ratio (lod score) of 5.65 at the CYP2A locus. These results indicate that human and porcine MH are most probably due to mutations in homologous genes, and also provide a potentially accurate and noninvasive method of diagnosis for MHS.
恶性高热（MH）是一种遗传性人类骨骼肌疾病，是麻醉导致死亡的主要原因之一。据报道，MH的发病率在儿童中为1/12000，在成人中为1/40000。所有常用的吸入性麻醉剂都会在易感人群中引发MH；其特征是肌肉代谢显著加速、挛缩、体温过高和心动过速。通过对活检获得的肌肉组织进行挛缩试验来预测对MH的易感性（MHS）。猪中存在一种几乎相同的疾病，称为猪恶性高热。对猪综合征的遗传学进行了广泛研究；控制猪恶性高热表达的基因座与磷酸葡萄糖异构酶基因座（GPI）存在遗传联系。在人类中，GPI已被定位到19号染色体的q12 - 13.2区域（参考文献10 - 12）。我们现在研究了几个爱尔兰大家庭中的遗传连锁关系，其中MHS作为常染色体显性性状进行分离。在此我们显示，在细胞色素P450 2A（CYP2A）基因座处，MHS与来自人类19号染色体GPI区域的DNA标记之间存在连锁关系，最大对数似然比（lod值）为5.65。这些结果表明，人类和猪的恶性高热很可能是由同源基因突变引起的，并且还为MHS提供了一种潜在准确且非侵入性的诊断方法。
