LIDDLES SYNDROME - HERITABLE HUMAN HYPERTENSION CAUSED BY MUTATIONS IN THE BETA-SUBUNIT OF THE EPITHELIAL SODIUM-CHANNEL
LIDDLES SYNDROME - HERITABLE HUMAN HYPERTENSION CAUSED BY MUTATIONS IN THE BETA-SUBUNIT OF THE EPITHELIAL SODIUM-CHANNEL
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DOI：
10.1016/0092-8674(94)90250-x
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发表时间：
1994-11-04
期刊：
影响因子：
64.5
通讯作者：
LIFTON, RP
中科院分区：
文献类型：
--
作者：
SHIMKETS, RA;WARNOCK, DG;LIFTON, RP
利德尔综合征(假醛固酮增多症)是人类高血压的一种常染色体显性遗传形式，其特征是一系列发现表明对阿米洛利敏感的远端肾上皮钠通道发生结构性激活。我们证明了编码上皮钠通道β亚基的基因与利德尔综合征在利德尔的原始亲属中是完全连锁的。对该基因的分析显示，在受影响的受试者中，一个过早终止密码子会截断编码蛋白的细胞质羧基末端。对来自另外四个家族的利德尔综合征受试者的分析表明，在所有四个家族中，要么提前终止，要么在这个相同的羧基末端区域发生移码突变。这些发现表明，利德尔综合征是由上皮性钠通道的β亚基突变引起的，并与该上皮离子通道的调节以及血压的动态平衡有关。
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.