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 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.
Hansson
J H
JH
Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut 06510, USA.
Nelson-Williams
C
C
Suzuki
H
H
Schild
L
L
Shimkets
R
R
Lu
Y
Y
Canessa
C
C
Iwasaki
T
T
Rossier
B
B
Lifton
R P
RP
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000172:deficiency; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation; D005796:Genes; D005799:Genes, Dominant; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D007008:Hypokalemia / Q000235:genetics; D015640:Ion Channel Gating / Q000235:genetics*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010375:Pedigree; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012083:Renin / Q000172:deficiency; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D012982:Sodium, Dietary / Q000009:adverse effects*; D013577:Syndrome; D013728:Terminator Regions, Genetic; D014982:Xenopus laevis
D003062:Codon; D053503:Epithelial Sodium Channels; D011993:Recombinant Fusion Proteins; C507048:SCNN1B protein, human; D015222:Sodium Channels; D012982:Sodium, Dietary; D000450:Aldosterone; D012083:Renin