Background The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease characterized by congenital mineralocorticoid resistance of the kidney. Twenty two different loss-of-function mutations in the MR gene have been described in families with PHA1. These mutations were not recurrent and resulted in a large phenotypic variability.

Objective To analyze the recurrence of an inactivating mutation in the MR gene in unrelated families with autosomal dominant PHA1.

Patients Seventeen members from three unrelated families with autosomal dominant PHA1 were studied, including eleven affected patients with variable clinical manifestations. Fifty healthy subjects were used as controls.

Methods Genomic DNA was extracted and the entire coding region of the MR gene was submitted to automatic sequencing. Four dinucleotide microsatellite markers spanning a region of 3.2 cM in the hMR gene locus and two intragenic polymorphisms were used for haplotype analysis.

Results A heterozygous point mutation at codon 947 (c.2839C>T) changing arginine to stop codon (R947X) was found in the three families. Different haplotypes segregated with the R947X mutation in each family, demonstrating the absence of a founder effect for this mutation.

Conclusion Codon 947 of the mineralocorticoid receptor is the first mutational hot spot for autosomal dominant PHA1.