A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1

J Clin Endocrinol Metab. 2000 Dec;85(12):4690-4. doi: 10.1210/jcem.85.12.7078.


Pseudohypoaldosteronism type 1 (PHA1) is a rare condition characterized by neonatal salt loss with dehydration, hypotension, hyperkalemia, and metabolic acidosis, despite elevated plasma aldosterone levels and PRA. Two modes of inheritance of PHA1 have been described: an autosomal dominant form and an autosomal recessive form. An autosomal recessive form manifests severe life-long salt wasting resulting from multiple mineralocorticoid target tissue such as sweat, salivary glands, the colonic epithelium, and lung. Contrary, an autosomal dominant PHA1 manifests milder salt wasting that gradually improves with advancing age. Recently, in one sporadic and four dominant cases, four different mutations including two frame shift mutations, two premature termination codons, and one splice site mutation in the mineralocorticoid receptor (MR) gene were identified. We studied the molecular mechanisms of one Japanese family with a renal form of PHA1. PCR and direct sequencing of the MR gene identified a heterozygous point mutation changing codon 924 Leu (CTG) to CCG (Pro) (L924P) in all affected members. COS-1 cells were transfected with expression vectors for either wild type or the mutant MR-L924P receptors, together with the reporter plasmid (glucocorticoid response element tk-CAT). Aldosterone increased CAT activity in cells expressing wild-type receptor, but had no effect in cells expressing the mutant receptors. These results suggest that mineralocorticoid resistance in this family is due to a missense mutation in the MR gene. To our knowledge, this is the first case of the missense mutation of the MR gene in renal PHA1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aldosterone / blood
  • Child
  • Exons / genetics
  • Female
  • Gene Deletion
  • Humans
  • Infant
  • Infant, Newborn
  • Ligands
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree
  • Pseudohypoaldosteronism / genetics*
  • Receptors, Mineralocorticoid / genetics*


  • Ligands
  • Receptors, Mineralocorticoid
  • Aldosterone