Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.
AUTOR(ES)
Tamura, H
RESUMO
Mutations in beta or gamma subunit of the epithelial sodium channel (ENaC) have been found to cause a hereditary form of human hypertension, Liddle syndrome. Most of the mutations reported are either nonsense mutations or frame shift mutations which would truncate the cytoplasmic carboxyl terminus of the beta or gamma subunits of the channel, suggesting that these domains are important for the normal regulation of this channel. We sequenced ENaC in a family with Liddle syndrome and found a missense mutation in beta subunit which predicts substitution of Tyr by His at codon 618, 2 bp downstream from a missense mutation (P616L) that has been reported recently. Presence of this mutation correlates with the clinical manifestations (hypertension, hypokalemia, suppressed aldosterone secretion) in this kindred. Functional expression studies in the Xenopus oocytes revealed constitutive activation of the Y618H mutant indistinguishable from that observed for the deletion mutant (R564stop) identified in the original pedigree of Liddle. Our data suggest that the region between Pro616 and Tyr618 is critically important for regulation of ENaC activity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=507244Documentos Relacionados
- The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel.
- A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity.
- A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.
- A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene.
- Myasthenic syndrome caused by mutation of the SCN4A sodium channel