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Pseudohypoaldosteronism type IB1 is an autosomal recessive salt-wasting disorder characterized by failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis due to reduced epithelial sodium channel activity. A 32-year-old female presented with persistent hyperkalemia, metabolic acidosis and failure to thrive and was found to carry compound heterozygous SCNN1B variants c.1288del (p.Leu430TyrfsTer3) and c.1466+1G>A, confirming the diagnosis (PMID:26807262). This single unrelated proband provides limited genetic evidence, with biallelic loss-of-function alleles likely abolishing β-ENaC function. No functional assays have been reported for these specific β-ENaC variants, although the clinical phenotype is concordant with channel loss-of-function. Additional unrelated cases, segregation data, and in vitro studies are required to substantiate this association. Key take-home: targeted SCNN1B sequencing in neonates with PHA1 phenotype enables accurate diagnosis and guides management of life-threatening electrolyte imbalances.
Gene–Disease AssociationLimitedOne unrelated proband with compound heterozygous LoF SCNN1B variants (c.1288del, c.1466+1G>A) ([PMID:26807262]) Genetic EvidenceLimitedBiallelic loss-of-function variants identified in a single proband with no segregation or replication Functional EvidenceLimitedNo published functional assays for β-ENaC SCNN1B PHA1 variants; presumed loss-of-function |