| A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1. | |
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MedLine Citation:
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PMID: 21653223 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disorder of mineralocorticoid resistance characterized by salt wasting, hyperkalemia, high aldosterone levels and failure to thrive. An autosomal recessive form (AR-PHA1) is caused by mutations in the epithelial sodium channel ENaC with usually severe and persisting multi-organ symptoms. The autosomal dominant form of PHA1 (AD-PHA1) is due to mutations in the mineralocorticoid receptor causing milder and transient symptoms restricted to the kidney. We identified a homozygous missense mutation in the SCNN1A gene (c.727T>C/p.Ser243Pro), encoding α subunit of ENaC (αENaC) in a prematurely-born boy with a severe salt-losing syndrome. The patient improved rapidly under treatment and dietary salt supplementation could be stopped after 6 months. Interestingly his sibling born at term and harboring the same homozygous Ser243Pro mutation, showed no symptom of salt-losing nephropathy. In vitro expression of the αSer243Pro ENaC mutant revealed a slight but significant decrease in ENaC activity that is exacerbated in the presence of high Na+ load. Our study provides the first evidence that ENaC activity is critical for the maintenance of salt balance in the immature kidney of preterm babies. Together with previous studies, it shows that, when the kidney is fully mature, the severity of the symptoms of AR-PHA1 is related to the degree of the ENaC loss of function. Finally, this study identifies a novel functional domain in the extracellular loop of ENaC. |
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Authors:
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Mirjam Dirlewanger; Delphine Huser; Maria-Christina Zennaro; Eric Girardin; Laurent Schild; Valerie M Schwitzgebel |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-7 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: - ISSN: 1522-1555 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Geneva. |
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