A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1.

Détails

ID Serval
serval:BIB_9FF54298A017
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1.
Périodique
American Journal of Physiology. Endocrinology and Metabolism
Auteur(s)
Dirlewanger M., Huser D., Zennaro M.C., Girardin E., Schild L., Schwitzgebel V.M.
ISSN
1522-1555 (Electronic)
ISSN-L
0193-1849
Statut éditorial
Publié
Date de publication
2011
Volume
301
Numéro
3
Pages
E467-E473
Langue
anglais
Résumé
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 multiorgan 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.Ser(243)Pro), encoding α-subunit of ENaC (α-ENaC) 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 mo. Interestingly, the patient's sibling born at term and harboring the same homozygous Ser(243)Pro mutation showed no symptom of salt-losing nephropathy. In vitro expression of the αSer(243)Pro 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.
Mots-clé
Epithelial Sodium Channel/genetics, Female, Homozygote, Humans, Infant, Newborn, Infant, Premature, Male, Mutation, Missense, Pseudohypoaldosteronism/genetics
Pubmed
Web of science
Création de la notice
09/09/2011 11:42
Dernière modification de la notice
20/08/2019 16:06
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