Journal article
Systemic pseudohypoaldosteronism from deletion of the promoter region of the human Beta epithelial na(+) channel subunit
American journal of respiratory cell and molecular biology, Vol.27(3), pp.314-319
09/2002
DOI: 10.1165/rcmb.2002-0029OC
PMID: 12204893
Abstract
Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder that arises from loss of function mutations of the alpha, beta, or gamma 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 betaENaC 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 betaENaC, we confirmed a large deletion (> 1,300 bp). In summary, a homozygous mutation in the promoter region of betaENaC leads to PHAI, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype.
Details
- Title: Subtitle
- Systemic pseudohypoaldosteronism from deletion of the promoter region of the human Beta epithelial na(+) channel subunit
- Creators
- Christie P Thomas - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1081, USA. christie-thomas@uiowa.eduJackie ZhouKang Z LiuVerity E MickEithne MacLaughlinMichael Knowles
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.27(3), pp.314-319
- Publisher
- United States
- DOI
- 10.1165/rcmb.2002-0029OC
- PMID
- 12204893
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Grant note
- RR00046 / NCRR NIH HHS DK54348 / NIDDK NIH HHS HL34322 / NHLBI NIH HHS R01 DK054348 / NIDDK NIH HHS
- Language
- English
- Date published
- 09/2002
- Academic Unit
- Stead Family Department of Pediatrics; Obstetrics and Gynecology; Nephrology; Internal Medicine
- Record Identifier
- 9983986082202771
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