31904
title and abstract
Pseudohypoaldosteronism type 1 and the genes encoding prostasin, alpha-spectrin, and Nedd4.
Pseudohypoaldosteronism type 1 (PHA1), a rare disorder of infancy, presents with potential life-threatening salt wasting and failure to thrive. Thus far, PHA1 has been attributed to mutations affecting the mineralocorticoid receptor or any of the three subunits assembling the amiloride-sensitive epithelial sodium channel (ENaC). However, a lot of patients with a phenotype resembling PHA1, show no defects in these proteins, making it likely that further genes are involved in the aetiology of this disease. Recent studies have elucidated additional participants (alpha-spectrin and members of the families of transmembrane serine proteases, ubiquitin-protein ligases, and serum- and glucocorticoid-regulated kinases, respectively) regulating and/or interacting in the complex pathway of sodium retention in the amiloride-sensitive distal nephron. This led us to investigate whether PHA1 can also be associated with mutations in some of these genes. Our data suggest that at least the prostasin gene might be excluded as a causative locus.