Ptácek L J, George A L, Griggs R C, Tawil R, Kallen R G, Barchi R L, Robertson M, Leppert M F
Department of Neurology, Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt Lake City 84132.
Cell. 1991 Nov 29;67(5):1021-7. doi: 10.1016/0092-8674(91)90374-8.
DNA from seven unrelated patients with hyperkalemic periodic paralysis (HYPP) was examined for mutations in the adult skeletal muscle sodium channel gene (SCN4A) known to be genetically linked to the disorder. Single-strand conformation polymorphism analysis revealed aberrant bands that were unique to three of these seven patients. All three had prominent fixed muscle weakness, while the remaining four did not. Sequencing the aberrant bands demonstrated the same C to T transition in all three unrelated patients, predicting substitution of a highly conserved threonine residue with a methionine in a membrane-spanning segment of this sodium channel protein. The observation of a distinct mutation that cosegregates with HYPP in two families and appears as a de novo mutation in a third establishes SCN4A as the HYPP gene. Furthermore, this mutation is associated with a form of HYPP in which fixed muscle weakness is seen.
对7名患有高钾性周期性麻痹（HYPP）的无亲缘关系患者的DNA进行了检测，以查找已知与该疾病存在遗传关联的成人骨骼肌钠通道基因（SCN4A）中的突变。单链构象多态性分析显示出异常条带，这些条带是这7名患者中的3名所特有的。这3名患者均有明显的固定性肌肉无力，而其余4名患者则没有。对异常条带进行测序显示，所有3名无亲缘关系的患者中均出现了相同的从C到T的转变，这预示着在该钠通道蛋白的一个跨膜区段中，一个高度保守的苏氨酸残基被甲硫氨酸取代。在两个家族中观察到与HYPP共分离且在第三个家族中表现为新发突变的一个独特突变，确定了SCN4A为HYPP基因。此外，该突变与一种伴有固定性肌肉无力的HYPP形式相关。
