The term "Bartter's syndrome" comprises a set of autosomal recessively inherited 
renal tubular disorders characterized by hypokalemia, metabolic alkalosis, 
hyperreninism, and hyperaldosteronism but normal blood pressure. Additional 
clinical and biochemical features led to a classification into phenotypically 
different tubulopathies: Gitelman's syndrome, hyperprostaglandin E syndrome 
(antenatal Bartter's syndrome), and classic Bartter's syndrome. Gitelman's 
syndrome results from mutations in the SLC12A3 gene encoding the human 
thiazide-sensitive sodium chloride cotransporter, leading to impaired 
reabsorption of sodium chloride in the distal convoluted tubule. Genetic 
heterogeneity of hyperprostaglandin E syndrome has been demonstrated by 
identification of mutations in the SLC12A1 gene as well as in the KCNJ1 gene. 
Mutations in SLC12A1 coding for the bumetanide-sensitive sodium potassium 2 
chloride cotransporter (NKCC2) cause defective reabsorption of sodium chloride 
in the thick ascending limb of Henle's loop. Mutations in KCNJ1 leading to loss 
of function of the potassium channel ROMK disrupt potassium recycling back to 
the tubule lumen and inhibit thereby the NKCC2 activity. A third gene for 
hyperprostaglandin E syndrome has been mapped to the short arm of chromosome 1, 
and it remains to be evaluated whether other genes are involved in the 
pathogenesis of this disease. Classic Bartter's syndrome has been demonstrated 
to result from defective chloride transport across the basolateral membrane in 
the distal nephron due to mutations in the chloride channel gene CLCNKB. This 
article reviews the molecular genetic approach that has led to identification of 
genetic defects underlying the different hypokalemic tubulopathies.