Shimkets R A, Warnock D G, Bositis C M, Nelson-Williams C, Hansson J H, Schambelan M, Gill J R, Ulick S, Milora R V, Findling J W
Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Cell. 1994 Nov 4;79(3):407-14. doi: 10.1016/0092-8674(94)90250-x.
Liddle's syndrome (pseudoaldosteronism) is an autosomal dominant form of human hypertension characterized by a constellation of findings suggesting constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel. We demonstrate complete linkage of the gene encoding the beta subunit of the epithelial sodium channel to Liddle's syndrome in Liddle's original kindred. Analysis of this gene reveals a premature stop codon that truncates the cytoplasmic carboxyl terminus of the encoded protein in affected subjects. Analysis of subjects with Liddle's syndrome from four additional kindreds demonstrates either premature termination or frameshift mutations in this same carboxy-terminal domain in all four. These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis.
利德尔综合征（假性醛固酮增多症）是一种常染色体显性遗传性人类高血压疾病，其特征是一系列表现提示对氨氯地平敏感的远端肾上皮钠通道发生持续性激活。我们在利德尔最初的家族中证实了编码上皮钠通道β亚基的基因与利德尔综合征完全连锁。对该基因的分析显示，在受影响的个体中存在一个过早的终止密码子，该密码子截断了所编码蛋白质的胞质羧基末端。对来自另外四个家族的利德尔综合征患者的分析表明，在所有四个家族中，该相同的羧基末端结构域均存在过早终止或移码突变。这些发现表明，利德尔综合征是由上皮钠通道β亚基的突变引起的，并且对该上皮离子通道的调节以及血压稳态具有重要意义。
