The term "Bartter syndrome" encompasses a group of closely related inherited 
tubulopathies characterized by markedly reduced NaCl transport by the distal 
nephron. At present, five different genetic variants have been demonstrated. The 
majority of patients with so-called classic Bartter syndrome carry inactivating 
mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel 
(Bartter syndrome type III). The purpose of this study was to investigate the 
underlying mutation in cases of classic Bartter syndrome followed at our center. 
Ten patients, including two sisters, with clinical and biochemical features of 
classic Bartter syndrome were included in the mutational analysis. They 
originated from different regions of Spain with either Basque or Spanish 
ancestry. There was no history of consanguineous marriage in any of the 
kindreds. The parents and siblings of each patient, as well as a population of 
300 healthy control adult subjects, were also analyzed. All ten patients were 
found to be homozygous for an identical missense mutation in the CLCNKB gene, 
substituting a threonine for an alanine at codon 204 (A204T) in the putative 
fifth transmembrane domain of the protein. None of the 300 control subjects were 
homozygous for the A204T allele. Overall, the A204T mutation was detected on 
2/600 control chromosomes. Despite sharing a common mutation, the clinical 
manifestations of the syndrome in the patients varied from lack of symptoms to 
severe growth retardation. Demonstration of a point mutation within the CLCNKB 
gene as the apparently unique cause of Bartter syndrome type III in Spain is 
highly suggestive of a founder effect. Our results also support the lack of 
correlation between genotype and phenotype in this disease.