UNIGE document Scientific Article
previous document  unige:25735  next document
add to browser collection
Title

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

Authors
Huser, Delphine
Zennaro, Maria-Christina
Schild, Laurent
Published in American Journal of Physiology. Endocrinology and Metabolism. 2011, vol. 301, no. 3, p. E467-73
Abstract 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.
Keywords Epithelial Sodium Channels/geneticsFemaleHomozygoteHumansInfant, NewbornInfant, PrematureMaleMutation, MissensePseudohypoaldosteronism/genetics
Identifiers
PMID: 21653223
Full text
Article (Published version) (596 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Pathogénèse du syndrome néphrotique idiopathique de l'enfant (180)
Diabète et métabolisme (178)
Citation
(ISO format)
DIRLEWANGER, Mijam et al. A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1. In: American Journal of Physiology. Endocrinology and Metabolism, 2011, vol. 301, n° 3, p. E467-73. https://archive-ouverte.unige.ch/unige:25735

249 hits

0 download

Update

Deposited on : 2013-01-18

Export document
Format :
Citation style :