HYPERTENSION CAUSED BY A TRUNCATED EPITHELIAL SODIUM-CHANNEL GAMMA-SUBUNIT - GENETIC-HETEROGENEITY OF LIDDLE SYNDROME
HYPERTENSION CAUSED BY A TRUNCATED EPITHELIAL SODIUM-CHANNEL GAMMA-SUBUNIT - GENETIC-HETEROGENEITY OF LIDDLE SYNDROME
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DOI：
10.1038/ng0995-76
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发表时间：
1995-09-01
期刊：
影响因子：
30.8
通讯作者：
LIFTON, RP
中科院分区：
文献类型：
--
作者：
HANSSON, JH;NELSONWILLIAMS, C;LIFTON, RP
高血压患者的血压对饮食中盐的敏感性是一个共同的特点。这些特征由孟德尔疾病Liddle综合征举例说明，先前显示由肾上皮钠通道的组成性激活引起，所述组成性激活是由于该通道的β亚基中的突变。我们现在证明，这种疾病也可能是由于突变截短该通道的γ亚基的羧基末端;这种截短的亚基也激活通道活性。这些发现表明Liddle综合征的遗传异质性，表明β和γ亚基在通道活性负调控中的独立作用，并确定了一个新的基因，其中突变导致盐敏感型人类高血压。
Sensitivity of blood pressure to dietary salt is a common feature in subjects with hypertension. These features are exemplified by the mendelian disorder, Liddle's syndrome, previously shown to arise from constitutive activation of the renal epithelial sodium channel due to mutation in the beta subunit of this channel. We now demonstrate that this disease can also result from a mutation truncating the carboxy terminus of the gamma subunit of this channel; this truncated subunit also activates channel activity. These findings demonstrate genetic heterogeneity of Liddle's syndrome, indicate independent roles of beta and gamma subunits in the negative regulation of channel activity, and identify a new gene in which mutation causes a salt-sensitive form of human hypertension.