title: Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.
abstract: Mutations in the Na-K-2Cl cotransporter (NKCC2), a mediator of renal salt reabsorption, cause Bartter's syndrome, featuring salt wasting, hypokalaemic alkalosis, hypercalciuria and low blood pressure. NKCC2 mutations can be excluded in some Bartter's kindreds, prompting examination of regulators of cotransporter activity. One regulator is believed to be ROMK, an ATP-sensitive K+ channel that 'recycles' reabsorbed K+ back to the tubule lumen. Examination of the ROMK gene reveals mutations that co-segregate with the disease and disrupt ROMK function in four Bartter's kindreds. Our findings establish the genetic heterogeneity of Bartter's syndrome, and demonstrate the physiologic role of ROMK in vivo.
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
authors.initials: J
authors.lastname: Rodriguez-Soriano
authors.forename: J H
authors.initials: JH
authors.lastname: Hamdan
authors.forename: A
authors.initials: A
authors.lastname: DiPietro
authors.forename: H
authors.initials: H
authors.lastname: Trachtman
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 / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry; D003241:Consanguinity; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D028021:Sodium-Potassium-Chloride Symporters
chemical_list: D002352:Carrier Proteins; C086989:KCNJ1 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D028021:Sodium-Potassium-Chloride Symporters