Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families.
Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families.
复制标题
将编码 L 型电压依赖性钙通道的 α2/δ 亚基的基因定位到染色体 7q，并分析恶性高热易感家族中侧翼标记的分离。
DOI：
10.1093/hmg/3.6.969
复制
发表时间：
1994
影响因子：
3.5
通讯作者：
Ellis,FR
中科院分区：
文献类型：
--
作者：
Iles,DE;Lehmann-Horn,F;Scherer,SW;Tsui,LC;OldeWeghuis,D;Suijkerbuijk,RF;Heytens,L;Mikala,G;Schwartz,A;Ellis,FR
恶性高热易感性（MHS）是一种常染色体显性遗传的骨骼肌疾病，表现为由常用麻醉剂引发的潜在致命的高代谢危象。MHS遗传异质性的这一证明促使人们研究钙调节蛋白而不是兰尼碱受体（RYR 1）所起的作用，迄今为止，在不到一半的欧洲MHS家族研究中，RYR 1与MHS有关。以前，我们已经排除了编码骨骼肌L型电压依赖性钙通道α1-、β1-和γ-亚基的基因作为MHS的候选基因。本文报道了编码α2/δ-亚基的基因CACNL 2A的克隆和部分DNA序列分析，并对其在染色体7 q近端长臂上的定位进行了研究。在D 7S 849位点发现了一个新的与CACNL 2A相近的二核苷酸重复标记，并在6个MHS家系中进行了连锁检测。D 7S 849和侧翼遗传标记与MHS位点共分离，在一个三代家系中通过11次减数分裂。这些结果表明，在CACNL 2A或附近的突变可能涉及这种异质性疾病的某些形式。
Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents. This demonstration of genetic heterogeneity in MHS prompted the investigation of the roles played by calcium regulatory proteins other than the ryanodine receptor (RYR1), which is known to be linked to MHS in fewer than half of the European MHS families studies to date. Previously, we have excluded the genes encoding the skeletal muscle L-type voltage-dependent calcium channel α1-, β1-and γ-subunits as candidates for MHS. In this report, we describe the cloning and partial DNA sequence analysis of the gene encoding the α2/δ-subunits, CACNL2A, and its localization onthe proximal long arm of chromosome 7q. A new dinucleotide repeat marker close to CACNL2A was identified at the D7S849 locus and tested for linkage in six MHS families. D7S849 and flanking genetic markers were found to co-segregate with the MHS locus through 11 meioses in one, three-generation family. These results suggest that mutations in or near CACNL2A may be involved in some forms of this heterogeneous disorder.