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No apparent mineralocorticoid receptor defect in a series of sporadic cases of pseudohypoaldosteronism

par Arai, Keiko;Tsigos, Constantine;Suzuki, Yoshifumi;Listwak, Sam;Zachman, Keith;Zangeneh, Fereydoun;Rapaport, Robert;Chanoine, Jean-Pierre ;Chrousos, GEORGE Panagiotis
Référence The Journal of clinical endocrinology and metabolism, 80, 3, page (814-817)
Publication Publié, 1995

Article révisé par les pairs

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Résumé :

Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944→T944, Ala241→Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760→G760, Ileu180→Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone. © 1995 by The Endocrine Society.