Db. Simon et al., BARTTERS-SYNDROME, HYPOKALEMIC ALKALOSIS WITH HYPERCALCIURIA, IS CAUSED BY MUTATIONS IN THE NA-K-2CL COTRANSPORTER NKCC2, Nature genetics, 13(2), 1996, pp. 183-188
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.