Exclusion of Serum- and Glucocorticoid-Induced Kinase 1 (SGK1) as a Candidate Gene for Genetically Heterogeneous Renal Pseudohypoaldosteronism Type I in Eight Families
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Media type:
E-Article
Title:
Exclusion of Serum- and Glucocorticoid-Induced Kinase 1 (SGK1) as a Candidate Gene for Genetically Heterogeneous Renal Pseudohypoaldosteronism Type I in Eight Families
Contributor:
Riepe, Felix G.;
Holterhus, Paul-Martin
Description:
<jats:p><i>Objective:</i> Autosomal-dominant pseudohypoaldosteronism type 1 (PHA1) is mostly caused by mutations in the mineralocorticoid receptor <i>(NR3C2)</i> gene. However, several kindreds with clinical signs of PHA1 but without <i>NR3C2</i> gene mutations or deletions are reported. Serum- and glucocorticoid-induced kinase 1 (Sgk1) is involved in epithelial sodium reabsorption by facilitating the accumulation of the epithelial sodium channel in the plasma membrane. Therefore variations in the <i>SGK1</i> gene may aggravate renal salt loss or cause PHA1. <i>Methods:</i> The <i>SGK1</i> genewas sequenced in 10 patients with the typical clinical signs of PHA1 but without <i>NR3C2 </i>or <i>SCNN1A</i>, <i>SCNN1B</i> and <i>SCNN1C</i> gene mutation. <i>Results:</i> No disease-causing <i>SGK1</i> gene mutation was detected in the studied PHA1 patient group. Two novel intronic SNPs which were also present in the normal population were detected in 2 patients. <i>Conclusion:</i> Our data do not support that <i>SGK1</i> gene variations are disease-causing factors in genetically unexplained PHA1. Therefore, systematic investigation of other factors downstream of the MR involved in epithelial sodium reabsorption is warranted in patients with autosomal-dominant PHA1.</jats:p>