Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q.
Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q.
复制标题
恶性高热易感位点 (MHS2) 定位于人类染色体 17q 的证据。
DOI：
10.1016/s0888-7543(05)80152-1
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发表时间：
1992
期刊：
影响因子：
4.4
通讯作者：
Meyers,DA
中科院分区：
文献类型：
--
作者：
Levitt,RC;Olckers,A;Meyers,S;Fletcher,JE;Rosenberg,H;Isaacs,H;Meyers,DA
恶性高热易感性是一种致命的常染色体显性骨骼肌代谢障碍，由所有强效吸入麻醉气体引发。最近的连锁研究表明，这种疾病的遗传位点位于19q13.1上。我们以前曾报道过三个不相关的家庭被诊断为MHS是不相关的标记周围的19q13.1这个位点。在这份报告中，我们扩展这些观察，目前连锁研究16 MHS家庭。4个家系（25%）与19 q12-q13.2区域（Zmax= 2.96，ryanodine受体θ= 0.0）连锁。在染色体17q11.2-q24上发现5个家系（31%）与匿名标记NME 1（以前命名为NM 23）紧密连锁（Zmax= 3.26，θ= 0.0）。两个家庭（13%）显然是不连锁的这些染色体区域。在另外五个家庭中，数据不足以确定其连锁状态（它们可能与两个或更多个位点连锁）。我们的异质性分析的结果是一致的假设，MHS可以引起人类至少三个不同的遗传位点之一。此外，我们提供了初步的连锁数据表明，在人类MHS的基因定位到17 q11.2-q24（MHS 2），这个推定的基因座的基因频率约等于19 q上的MHS 1基因座。
Malignant hyperthermia susceptibility is a lethal autosomal dominant disorder of skeletal muscle metabolism that is triggered by all potent inhalation anesthetic gases. Recent linkage studies suggest a genetic locus for this disorder on 19q13.1. We have previously reported three unrelated families diagnosed with MHS that are unlinked to markers surrounding this locus on 19q13.1. In this report we extend these observations and present linkage studies on 16 MHS families. Four families (25%) were found linked to the region 19q12–q13.2 (Zmax= 2.96 with the ryanodine receptor atθ= 0.0). Five families (31%) were found closely linked to the anonymous marker NME1 (previously designated NM23) on chromosome 17q11.2–q24 (Zmax= 3.26 atθ= 0.0). Two families (13%) were clearly unlinked to either of these chromosomal regions. In five additional families, data were insufficient to determine their linkage status (they were potentially linked to two or more sites). The results of our heterogeneity analyses are consistent with the hypothesis that MHS can be caused in humans by any one of at least three distinct genetic loci. Furthermore, we provide preliminary linkage data suggesting the localization of a gene in human MHS to 17q11.2–q24 (MHS2), with a gene frequency of this putative locus approximately equal to that of the MHS1 locus on 19q.