Genetic Variants of Thiazide-Sensitive NaCl-Cotransporter in Gitelman’s Syndrome and Primary Hypertension
- 1 September 2000
- journal article
- other
- Published by Wolters Kluwer Health in Hypertension
- Vol. 36 (3) , 389-394
- https://doi.org/10.1161/01.hyp.36.3.389
Abstract
—Gitelman’s syndrome is an autosomal recessive disorder characterized by electrolyte disturbances and low blood pressure. The disease is caused by homozygous or compound heterozygous inactivating mutations in the thiazide-sensitive NaCl-cotransporter gene leading to reduced renal sodium reabsorption. We report 4 patients with Gitelman’s syndrome from southern Sweden, all in whom we identified compound heterozygous mutations in the thiazide-sensitive NaCl-cotransporter gene (Gly439Ser, Gly731Arg, Gly741Arg, Thr304Pro, and 2745insAGCA), of which the latter 2 have not been described before. We hypothesized that such mutations in their heterozygous form protect against primary hypertension in the general population and that the gene may also harbor activating mutations that increase the risk for primary hypertension. Accordingly, the gene was screened for mutations in 20 patients with primary hypertension and in 20 normotensive subjects by single-strand conformation polymorphism and direct DNA sequenc...Keywords
This publication has 22 references indexed in Scilit:
- Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type IIINature Genetics, 1997
- Genetic heterogeneity of Barter's syndrome revealed by mutations in the K+ channel, ROMKNature Genetics, 1996
- Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na–K–2CI cotransporter NKCC2Nature Genetics, 1996
- Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1Nature Genetics, 1996
- Gitelman's variant of Barter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na–Cl cotransporterNature Genetics, 1996
- Human hypertension caused by mutations in the kidney isozyme of 11β–hydroxysteroid dehydrogenaseNature Genetics, 1995
- A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.Proceedings of the National Academy of Sciences, 1995
- Liddle's syndrome: Heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channelCell, 1994
- Finding genes that cause human hypertensionJournal Of Hypertension, 1993
- A chimaeric llβ-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertensionNature, 1992