Autosomal-dominant pseudohypoaldosteronism type 1 in a Turkish family is associated with a novel nonsense mutation in the human mineralocorticoid receptor gene.

Pseudohypoaldosteronism type 1 (PHA1) is a rare congenital disease inherited in either an autosomal-recessive or an autosomal-dominant trait. The autosomal-dominant form manifests with renal salt loss in infancy and a gradual improvement with advancing age. PHA1 presents with potential life-threatening salt wasting and failure to thrive in early infancy. Autosomal-dominant forms of PHA1 are often caused by heterozygous mutations of the MR gene coding for the mineralocorticoid receptor. Whether heterozygous mutations of the MR gene impair biological function as a result of haplo-insufficiency or due to a dominant-negative effect needs further clarification. We report a case of a renal form of PHA1 in a Turkish family. A heterozygous nonsense mutation c3055C>T (R947X) in exon 9 of the MR gene leading to a premature stop codon was identified in the index patient. The truncated receptor is free of aldosterone binding. The segregation analysis revealed the identical mutation in the patient's father, who never showed any symptoms of PHA. This shows the incomplete penetrance of the phenotype, although a mild salt loss might have been overlooked in the father's childhood.