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

Abstract
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.
AuthorsK Arai, C Tsigos, Y Suzuki, S Listwak, K Zachman, F Zangeneh, R Rapaport, J P Chanoine, G P Chrousos
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 80 Issue 3 Pg. 814-7 (Mar 1995) ISSN: 0021-972X [Print] United States
PMID7883835 (Publication Type: Case Reports, Journal Article)
Chemical References
  • DNA, Complementary
  • Receptors, Mineralocorticoid
Topics
  • Adolescent
  • Base Sequence
  • Blotting, Southern
  • Child, Preschool
  • DNA, Complementary (chemistry)
  • Female
  • Humans
  • Infant
  • Male
  • Point Mutation
  • Polymorphism, Restriction Fragment Length
  • Pseudohypoaldosteronism (genetics)
  • Receptors, Mineralocorticoid (genetics)

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