Revealing a subclinical salt-losing phenotype in heterozygous carriers of the novel S562P mutation in the alpha subunit of the epithelial sodium channel.

Détails

ID Serval
serval:BIB_E00A92BEEFB4
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Revealing a subclinical salt-losing phenotype in heterozygous carriers of the novel S562P mutation in the alpha subunit of the epithelial sodium channel.
Périodique
Clinical Endocrinology
Auteur(s)
Riepe F.G., van Bemmelen M.X., Cachat F., Plendl H., Gautschi I., Krone N., Holterhus P.M., Theintz G., Schild L.
ISSN
1365-2265 (Electronic)
ISSN-L
0300-0664
Statut éditorial
Publié
Date de publication
2009
Volume
70
Numéro
2
Pages
252-258
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
OBJECTIVE: Pseudohypoaldosteronism type I (PHA1) is a rare inborn disease causing severe salt loss. Mutations in the three coding genes of the epithelial sodium channel (ENaC) are responsible for the systemic autosomal recessive form. So far, no phenotype has been reported in heterozygous carriers.
PATIENTS: A consanguineous family from Somalia giving birth to a neonate suffering from PHA1 was studied including clinical and hormonal characteristics of the family, mutational analysis of the SCNN1A, SCNN1B, SCNN1G and CFTR genes and in vitro analysis of the functional consequences of a mutant ENaC channel.
RESULTS: CFTR mutations have been excluded. SCNN1A gene analysis revealed a novel homozygous c.1684T > C mutation resulting in a S562P substitution in the alphaENaC protein of the patient. Functional analysis showed a significantly reduced S562P channel function compared to ENaC wild type. Protein synthesis and channel subunit assembly were not altered by the S562P mutation. Co-expression of mutant and wild-type channels revealed a dominant negative effect. In heterozygote carriers, sweat sodium and chloride concentrations were increased without additional hormonal or clinical phenotypes.
CONCLUSION: Hence, the novel mutation S562P is causing systemic PHA1 in the homozygous state. A thorough clinical investigation of the heterozygote SCNN1A mutation carriers revealed increased sweat sodium and chloride levels consistent with a dominant effect of the mutant S562P allele. Whether this subclinical phenotype is of any consequence for the otherwise asymptomatic heterozygous carriers has to be elucidated.
Mots-clé
Alleles, Chlorides/metabolism, Epithelial Sodium Channels/genetics, Female, Heterozygote, Humans, Infant, Newborn, Mutation, Missense/genetics, Pedigree, Phenotype, Pseudohypoaldosteronism/genetics, Pseudohypoaldosteronism/metabolism, Sodium/metabolism, Sweat/metabolism
Pubmed
Web of science
Création de la notice
04/01/2010 18:00
Dernière modification de la notice
20/08/2019 17:04
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