Faculty Collaboration Database

Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 1994 Nov 04;79(3):407-14

Date

11/04/1994

Pubmed ID

7954808

DOI

10.1016/0092-8674(94)90250-x

Scopus ID

2-s2.0-0027946089 (requires institutional sign-in at Scopus site)   1224 Citations

Abstract

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.

Author List

Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR Jr, Ulick S, Milora RV, Findling JW

Author

James W. Findling MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Base Sequence
Chromosome Mapping
Chromosomes, Human, Pair 16
Codon, Terminator
Epithelium
Female
Genetic Linkage
Genetic Markers
Humans
Hyperaldosteronism
Hypertension
Male
Molecular Sequence Data
Mutation
Reading Frames
Recombination, Genetic
Sodium Channels
Syndrome