title: Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2.
abstract: Inherited hypokalaemic alkalosis with low blood pressure can be divided into two groups-Gitelman's syndrome, featuring hypocalciuria, hypomagnesaemia and milder clinical manifestations, and Bartter's syndrome, featuring hypercalciuria and early presentation with severe volume depletion. Mutations in the renal Na-Cl cotransporter have been shown to cause Gitelman's syndrome. We demonstrate linkage of Bartter's syndrome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frameshift or non-conservative missense mutations for this gene that co-segregate with the disease. These findings demonstrate the molecular basis of Bartter's syndrome, provide the basis for molecular classification of patients with inherited hypokalaemic alkalosis, and suggest potential phenotypes in heterozygous carriers of NKCC2 mutations.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Simon
authors.forename: F E
authors.initials: FE
authors.lastname: Karet
authors.forename: J M
authors.initials: JM
authors.lastname: Hamdan
authors.forename: A
authors.initials: A
authors.lastname: DiPietro
authors.forename: S A
authors.initials: SA
authors.lastname: Sanjad
authors.forename: R P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D000595:Amino Acid Sequence; D001477:Bartter Syndrome / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D003241:Consanguinity; D018076:DNA, Complementary; D005260:Female; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D028021:Sodium-Potassium-Chloride Symporters
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D005819:Genetic Markers; D028021:Sodium-Potassium-Chloride Symporters