Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg R G, Hogan K, Powers P A, Lapie P, Vale-Santos J E, Weissenbach J
Department of Applied Physiology, University of Ulm, Germany.
Hum Mol Genet. 1994 Aug;3(8):1415-9. doi: 10.1093/hmg/3.8.1415.
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 arginine528. 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.
迄今为止报道的唯一钙通道突变是二氢吡啶受体α1亚基基因的缺失，导致肌肉发育不全小鼠出现新生儿死亡（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，低钾性周期性麻痹（HypoPP），也定位于同一区域（2）。对两名患者的cDNA进行测序发现，第1583位核苷酸发生了G到A的碱基交换，预测精氨酸528被组氨酸取代。这影响了跨膜片段IIS4中最外层的正电荷，该正电荷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个家族的患病成员中检测到了该突变。结果表明，二氢吡啶受体α1亚基突变导致了HypoPP。兴奋 - 收缩偶联的改变可能解释了肌肉无力的发生。
