title: 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.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: K
authors.initials: K
authors.lastname: Arai
authors.forename: C
authors.initials: C
authors.lastname: Tsigos
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Listwak
authors.forename: K
authors.initials: K
authors.lastname: Zachman
authors.forename: F
authors.initials: F
authors.lastname: Zangeneh
authors.forename: R
authors.initials: R
authors.lastname: Rapaport
authors.forename: J P
authors.initials: JP
authors.lastname: Chanoine
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D018076:DNA, Complementary / Q000737:chemistry; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011546:Pseudohypoaldosteronism / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D018161:Receptors, Mineralocorticoid