Journal Article

Functional Consequences of ROMK Mutants Linked to Antenatal Bartter's Syndrome and Implications for Treatment

Ruth A. Schwalbe, Laura Bianchi, Eric A. Accili and Arthur M. Brown

in Human Molecular Genetics

Volume 7, issue 6, pages 975-980
Published in print June 1998 | ISSN: 0964-6906
Published online June 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.6.975
Functional Consequences of ROMK Mutants Linked to Antenatal Bartter's Syndrome and Implications for Treatment

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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 phosphoryla-tion, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.

Journal Article.  4464 words.  Illustrated.

Subjects: Genetics and Genomics

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