title: A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel.
abstract: Liddle's syndrome is an autosomal dominant form of salt sensitive hypertension caused by mutations in the beta or gamma subunit of the epithelial sodium channel. Systematic mutagenesis studies revealed that a conserved PPPXY sequence (PY motif) of the C-terminus of the alpha, beta, or gamma subunits might be involved in the regulation of the channel activity. However, only two missense mutations in the PY motif of the beta subunit have been reported to cause Liddle's syndrome. We sequenced the C-termini of the beta and gamma subunits of the epithelial sodium channel in a Japanese family clinically diagnosed as having Liddle's syndrome and found a new missense mutation in the PY motif of the beta subunit, P615S. Expression studies with P615S mutant in Xenopus oocytes resulted in an about 3-fold increase in the amiloride-sensitive sodium current compared to the wild type (p = 0.001). These findings provide further clinical evidence for the hypothesis that a conserved PY motif may be critically important for the regulation of the epithelial sodium channel.
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Kumamoto University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Iwaoka
authors.forename: H
authors.initials: H
authors.lastname: Tokunaga
authors.forename: K
authors.initials: K
authors.lastname: Takamune
authors.forename: S
authors.initials: S
authors.lastname: Naomi
authors.forename: M
authors.initials: M
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Takahama
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000737:chemistry; D004848:Epithelium / Q000737:chemistry; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D016296:Mutagenesis; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011392:Proline / Q000235:genetics; D017422:Sequence Analysis, DNA; D012694:Serine / Q000235:genetics; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*; D013577:Syndrome
chemical_list: D003062:Codon; D015222:Sodium Channels; D012694:Serine; D004247:DNA; D011392:Proline