A CALCIUM-CHANNEL MUTATION CAUSING HYPOKALEMIC PERIODIC PARALYSIS
A CALCIUM-CHANNEL MUTATION CAUSING HYPOKALEMIC PERIODIC PARALYSIS
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DOI：
10.1093/hmg/3.8.1415
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发表时间：
1994-08-01
影响因子：
3.5
通讯作者：
FONTAINE, B
中科院分区：
文献类型：
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作者：
JURKATROTT, K;LEHMANNHORN, F;FONTAINE, B
迄今为止报道的唯一钙通道突变是 DHP 受体 α 1 亚基基因缺失，导致肌肉发育不良小鼠新生儿死亡 (1)。在人类中，该基因定位于染色体 1q31-32。一种常染色体显性肌肉疾病，即低钾性周期性麻痹 (HypoPP)，已被定位到同一区域 (2)。对两名患者的 cDNA 进行测序，发现 1583 号核苷酸发生 G 到 A 碱基交换，预示着精氨酸将被组氨酸取代 (528)。这会影响跨膜部分 IIS4 中最外层的正电荷，该部分被认为参与电压传感。通过限制性片段分析，在 25 个 HypoPP 家族中的 9 个受影响成员中检测到了该突变。结果表明，DHP 受体α1 亚基突变导致HypoPP。兴奋-收缩耦合的改变可以解释肌肉无力的发生。
The only calcium channel mutation reported to date is a deletion in the gene for the DHP-receptor alpha 1-subunit resulting in neonatal death in muscular dysgenesis mice (1). In humans, this gene maps to chromosome 1q31-32. An autosomal dominant muscle disease, hypokalemic periodic paralysis (HypoPP), has been mapped to the same region (2). Sequencing of cDNA of two patients revealed a G-to-A base exchange of nucleotide 1583 predicting a substitution of histidine for arginine(528). This affects the outermost positive charge in the transmembrane segment IIS4 that is considered to participate in voltage sensing. By restriction fragment analysis, the mutation was detected in the affected members of 9 out of 25 HypoPP families. The results indicate that the DHP-receptor alpha 1-subunit mutation causes HypoPP. An altered excitation - contraction coupling may explain the occurrence of muscle weakness.