No alteration in the primary structure of the mineralocorticoid receptor in a family with pseudohypoaldosteronism.

We have studied the molecular structure of the mineralocorticoid receptor (MR) complementary DNA (cDNA) in a kindred affected by pseudohypoaldosteronism (PHA). In this family, the clinical symptoms included salt wasting and failure to thrive, accompanied by high urinary levels of sodium despite hyponatremia, hyperkalemia and metabolic acidosis, elevation of PRA, and high plasma aldosterone levels. The patients were resistant to mineralocorticoid administration, but their symptoms ameliorated after a period of sodium supplementation, which was discontinued in older patients. Binding studies performed on mononuclear leukocytes of the members of the family have shown the absence of MR in two siblings and a marked reduction in another sibling of the father, suggesting either the absence of MR or a defect of the ligand-binding domain of the MR in these patients. Southern analysis of patient's DNA did not show any major rearrangement of the MR gene. To search for point mutations in the cDNA of the MR, we performed amplification of the MR cDNA by the polymerase chain reaction and direct sequencing of amplified products. No mutation was found in the entire coding sequence of the MR in patients affected by PHA. Although these results do not exclude a molecular abnormality present on the MR gene, they indicate that PHA in this family is not related to a modification of the MR primary structure.