A Large Consanguineous Family with a Mild and Transient Form of Autosomal Recessive Pseudohypoaldosteronism Type 1 (PHA1) Caused by a Novel Mutation in the SCNN1A Gene: Functional Studies

We present 12 patients from 4 different families with a mild and transient autosomal recessive PHA1 due to a novel homozygous missense mutation in the SCNN1A gene. Functional studies showed that the p.Phe226Cys substitution mutation in ENaC leads to a partial loss of function resulting mainly from both a decrease in the intrinsic ENaC activity, and a reduction in channel expression at the protein level. The partial loss of ENaC function could explain the mild phenotype, variable expressivity, and the transient course of the disorder in these patients.