HYPERTENSION CAUSED BY A TRUNCATED EPITHELIAL SODIUM-CHANNEL GAMMA-SUBUNIT - GENETIC-HETEROGENEITY OF LIDDLE SYNDROME

Sensitivity of blood pressure to dietary salt is a common feature in s ubjects with hypertension. These features are exemplified by the mende lian disorder, Liddle's syndrome, previously shown to arise from const itutive activation of the renal epithelial sodium channel due to mutat ion in the beta subunit of this channel. We now demonstrate that this disease can also result from a mutation truncating the carboxy terminu s of the gamma subunit of this channel; this truncated subunit also ac tivates channel activity. These findings demonstrate genetic heterogen eity of Liddle's syndrome, indicate independent roles of beta and gamm a subunits in the negative regulation of channel activity, and identif y a new gene in which mutation causes a salt-sensitive form of human h ypertension.