Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.
Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.
复制标题
日本高血压患者上皮钠通道β和γ亚基的六种错义突变。
作者：
K. Kamide;C. Tanaka;S. Takiuchi;Y. Miwa;M. Yoshii;T. Horio;Y. Kawano;T. Miyata
Liddle综合征是一种常染色体显性遗传疾病，其特征为钠敏感性早期高血压和由SCNN 1B和SCNN 1G编码的阿米洛利敏感性上皮钠通道的β或γ亚基突变。我们分别对948例和953例日本高血压患者的SCNN 1B外显子13的381 bp编码区和SCNN 1G外显子12的381 bp编码区进行测序。在SCNN 1B基因中，我们发现了三个杂合状态的错义突变，P592 S（n=3），T594 M（n=2）和E632 K（n=1），以及四个同义突变，Ile 515（n=1），Ser 520（n=19），Ser 533（n=1）和Thr 594（n=11）。在SCNN 1G基因中，我们发现了三个杂合状态的错义突变A578 V（n=1）、P603 S（n=1）和L 609 F（n=1），以及两个同义突变Ile 550（n=1）和Leu 649（n= 91，杂合; n=2，纯合）。我们没有发现以前在Liddle综合征激酶中报道的相同突变。6例SCNN 1B基因错义突变的高血压患者中有2例表现出非典型的肾素和醛固酮水平，尽管其中1例被诊断为肾血管性高血压。1例SCNN 1B基因中携带T594 M的患者对高血压具有抵抗性。在高血压患者中发现的这些SCNN 1B或SCNN 1G基因错义突变在高血压发病机制和电解质调节中的作用尚不清楚。因此，需要对这些突变进行进一步的研究，包括功能分析。
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.
DOI：
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发表时间：
1996-12
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
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作者：
Yan Ru Su;Mark Rutkowski;Charles A. Klanke;X. Wu;Y. Cui;Raymund Y. K. Pun;V. Carter;M. Reif;Anil G. Menon
通讯作者：
Yan Ru Su;Mark Rutkowski;Charles A. Klanke;X. Wu;Y. Cui;Raymund Y. K. Pun;V. Carter;M. Reif;Anil G. Menon