Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit.

Details

Serval ID
serval:BIB_7CD9222231C8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit.
Journal
Journal of Hypertension
Author(s)
Rossi E., Farnetti E., Debonneville A., Nicoli D., Grasselli C., Regolisti G., Negro A., Perazzoli F., Casali B., Mantero F., Staub O.
ISSN
0263-6352
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
26
Number
5
Pages
921-927
Language
english
Abstract
OBJECTIVE: The aim of the study was to search for mutations of SCNN1B and SCNN1G in an Italian family with apparently dominant autosomal transmission of a clinical phenotype consistent with Liddle's syndrome. METHODS: Genetic analysis was performed in the proband, his relatives, and 100 control subjects. To determine the functional role of the mutation identified in the proband, we expressed the mutant or wild-type epithelial sodium channel in Xenopus laevis oocytes. RESULTS: A novel point mutation, causing an expected substitution of a leucine residue for the second proline residue of the conserved PY motif (PPP x Y) of the beta subunit was identified in the proband. The functional expression of the mutant epithelial sodium channel in X. laevis oocytes showed a three-fold increase in the amiloride-sensitive current as compared with that of the wild-type channel. CONCLUSION: This newly identified mutation adds to other missense mutations of the PY motif of the beta subunit of the epithelial sodium channel, thus confirming its crucial role in the regulation of the epithelial sodium channel. To our knowledge, this is the first report of Liddle's syndrome in the Italian population, confirmed by genetic and functional analysis, with the identification of a gain-of-function mutation not previously reported.
Keywords
Adolescent, Adult, Animals, Base Sequence, Cells, Cultured, Epithelial Sodium Channel/genetics, Epithelial Sodium Channel/physiology, Female, Genetic Predisposition to Disease/genetics, Humans, Hypertension/genetics, Hypokalemia/genetics, Italy, Male, Mutation, Missense/genetics, Pedigree, Sodium/metabolism, Syndrome, Xenopus laevis
Pubmed
Web of science
Create date
14/01/2010 14:47
Last modification date
20/08/2019 14:38
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