NO ALTERATION IN THE PRIMARY STRUCTURE OF THE MINERALOCORTICOID RECEPTOR IN A FAMILY WITH PSEUDOHYPOALDOSTERONISM

We have studied the molecular structure of the mineralocorticoid recep tor (MR) complementary DNA (cDNA) in a kindred affected by pseudohypoa ldosteronism (PHA). In this family, the clinical symptoms included sal t wasting and failure to thrive, accompanied by high urinary levels of sodium despite hyponatremia, hyperkalemia and metabolic acidosis, ele vation of PRA, and high plasma aldosterone levels. The patients were r esistant to mineralocorticoid administration, but their symptoms ameli orated after a period of sodium supplementation, which was discontinue d in older patients. Binding studies performed on mononuclear leukocyt es of the members of the family have shown the absence of MR in two si blings and a marked reduction in another sibling and the father, sugge sting either the absence of MR or a defect of the ligand-binding domai n 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 m utations in the cDNA of the MR, we performed amplification of the MR c DNA by the polymerase chain reaction and direct sequencing of amplifie d 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 PH A in this family is not related to a modification of the MR primary st ructure.