BARTTERS-SYNDROME, HYPOKALEMIC ALKALOSIS WITH HYPERCALCIURIA, IS CAUSED BY MUTATIONS IN THE NA-K-2CL COTRANSPORTER NKCC2

Inherited hypokalaemic alkalosis with low blood pressure can be divide d into two groups - Gitelman's syndrome, featuring hypocalciuria, hypo magnesaemia and milder clinical manifestations, and Bartter's syndrome , featuring hypercalciuria and early presentation with severe volume d epletion. Mutations in the renal Na-Cl cotransporter have been shown t o cause Gitelman's syndrome. We demonstrate linkage of Bartter's syndr ome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frame shift or non-conservative missense mutations for this gene that co-seg regate with the disease. These findings demonstrate the molecular basi s of Bartter's syndrome, provide the basis for molecular classificatio n of patients with inherited hypokalaemic alkalosis, and suggest poten tial phenotypes in heterozygous carriers of NKCC2 mutations.