© 2002 American Thoracic Society DOI: 10.1165/rcmb.2002-0029OC Systemic Pseudohypoaldosteronism from Deletion of the Promoter Region of the Human ß Epithelial Na+ Channel SubunitDepartments of Internal Medicine, University of Iowa, Iowa City, Iowa; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Pediatrics, Children's Hospital and University of Southern California, Los Angeles, California Address correspondence to: Christie P. Thomas, Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242-1081. E-mail: christie-thomas{at}uiowa.edu
Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder that arises from loss of function mutations of the
Abbreviations: cystic fibrosis transmembrane regulator, CFTR • epithelial Na+ channel, ENaC • mineralocorticoid receptor, MR • pseudohypoaldosteronism type 1, PHAI • reverse transcriptase–polymerase chain reaction, RT-PCR This article has been cited by other articles:
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subunit of Epithelial Na+ Channel (ENaC). In addition to a severe renal phenotype in the neonatal period, patients with PHAI develop a childhood pulmonary syndrome characterized by cough and frequent respiratory infections. We tested a patient, born to consanguineous parents, who presented with dehydration, metabolic acidosis, hyperkalemia, elevated renin and aldosterone levels at birth, and recurrent respiratory symptoms in his first year. He demonstrated defective epithelial Na+ transport in multiple organs (raised sweat Cl-, 120 mM; raised salivary Na+ and Cl-, 118 and 111 mM, respectively; and little nasal amiloride-sensitive potential difference). No deleterious mutation was identified in the coding region of the three ENaC subunits. Reverse transcriptase-polymerase chain reaction of nasal epithelial RNA showed reduced ßENaC expression, and inability to amplify promoter elements indicated the possibility of a deletion in the 5' region. Using a probe that corresponded to exon 1A of ßENaC, we confirmed a large deletion (> 1,300 bp). In summary, a homozygous mutation in the promoter region of ßENaC leads to PHAI, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype. 
