Referenced in: none

Automatically associated channels: Kir1.1

Title: Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment.

Authors: R A Schwalbe, L Bianchi, E A Accili, A M Brown

Journal, date & volume: Hum. Mol. Genet., 1998 Jun , 7, 975-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9580661

Abstract
The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP-sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.