Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1.
Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1.
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进一步绘制恶性高热易感位点至染色体 3q13.1 的图谱。
DOI：
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发表时间：
1995
影响因子：
9.8
通讯作者：
Joël Lunardi
中科院分区：
文献类型：
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作者：
R. Sudbrak;Vincent Procaccio;Monica Klausnitzer;Julie L Curran;K. Monsieurs;C. Broeckhoven;Richard Ellis;Luc Heyetens;J. Hartung;Genevieve Kozak;Dorit Heilinger;Jean Weissenbach;Frank Lehman;R. Mueller;Thomas Deufel;A. D. Stewart;Joël Lunardi
恶性高热（MH）是一种潜在的致死性药物遗传学疾病，其MH易感性（MHS）以常染色体显性遗传特征传递。一个潜在的危及生命的MH危机是由暴露于常用的吸入麻醉剂和去极化肌肉松弛剂。在人类染色体19q13.1上发现了第一个恶性高热易感基因座（MHS 1），并已获得证据表明骨骼肌肌浆网钙释放通道（ryanodine受体; RYR 1）基因缺陷可导致某些形式的MH。然而，MH已被证明是遗传异质性的，并建议在染色体17 q和7 q上的额外位点。在人类基因组与多态性微卫星标记的协作搜索中，我们现在发现了MHS表型的连锁，如欧洲体外挛缩试验方案所评估的，与染色体3q13.1上定义1-cM间隔的标记。一个最大的多点lod得分为3.22，在一个单一的德国血统与经典的MH，并没有在这项研究中调查的其他家系显示该地区的连锁。排除了与MHS 1/RYR 1和染色体17 q和7 q上的推定位点的连锁。这项研究支持了MH存在相当大的遗传异质性的观点。
Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease for which MH susceptibility (MHS) is transmitted as an autosomal dominant trait. A potentially life-threatening MH crisis is triggered by exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. The first malignant hyperthermia susceptibility locus (MHS1) was identified on human chromosome 19q13.1, and evidence has been obtained that defects in the gene for the calcium-release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor; RYR1) can cause some forms of MH. However, MH has been shown to be genetically heterogeneous, and additional loci on chromosomes 17q and 7q have been suggested. In a collaborative search of the human genome with polymorphic microsatellite markers, we now found linkage of the MHS phenotype, as assessed by the European in vitro contracture test protocol, to markers defining a 1-cM interval on chromosome 3q13.1. A maximum multipoint lod score of 3.22 was obtained in a single German pedigree with classical MH, and none of the other pedigrees investigated in this study showed linkage to this region. Linkage to both MHS1/RYR1 and putative loci on chromosome 17q and 7q were excluded. This study supports the view that considerable genetic heterogeneity exists in MH.
恶性高热易感位点 (MHS2) 定位于人类染色体 17q 的证据。
影响因子：
4.4
作者：
Levitt,RC;Olckers,A;Meyers,S;Fletcher,JE;Rosenberg,H;Isaacs,H;Meyers,DA
通讯作者：
Meyers,DA