title: Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.
abstract: Liddle's syndrome is an autosomal dominant disease characterized by sodium-sensitive early hypertension and mutations in either the beta- or gamma-subunit of the amiloride-sensitive epithelial sodium channel encoded by SCNN1B and SCNN1G. We sequenced the 381 bp-coding regions in exon 13 of SCNN1B and the 381 bp-coding regions in exon 12 of SCNN1G in 948 and 953 Japanese patients with hypertension, respectively. In the SCNN1B gene, we identified three missense mutations, P592S (n=3), T594M (n=2), and E632K (n=1) in a heterozygous state in addition to four synonymous ones, Ile515 (n=1), Ser520 (n=19), Ser533 (n=1), and Thr594 (n=11). In the SCNN1G gene, we identified three missense mutations, A578V (n=1), P603S (n=1), and L609F (n=1) in a heterozygous state in addition to two synonymous ones, Ile550 (n=1) and Leu649 (n= 91, heterozygous; n=2, homozygous). We did not identify the same mutations previously reported in Liddle's syndrome kindreds. Two of the six hypertensive patients with missense mutation in the SCNN1B gene showed atypical renin and aldosterone levels, though one of them was diagnosed with renovascular hypertension. One patient with T594M in the SCNN1B gene was resistant to hypertension. The roles of these missense mutations in the SCNN1B or SCNN1G gene identified in hypertensive patients are not clear in the pathogenesis of hypertension and the regulation of electrolytes. Thus, further investigation of these mutations, including functional analyses, will be needed.
authors.affiliation: Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan. kamide@hsp.ncvc.go.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tanaka
authors.forename: Shin
authors.initials: S
authors.lastname: Takiuchi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yoshii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horio
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D044466:Asian People / Q000235:genetics*; D053503:Epithelial Sodium Channels; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D006978:Hypertension, Renovascular / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012083:Renin / Q000097:blood; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; C507052:SCNN1G protein, human; D015222:Sodium Channels; D000450:Aldosterone; D012083:Renin