henotypic spectrum of genetically confirmed Liddle syndrome is unknown, and some patients may remain undiagnosed and at risk of inefficient treatment. In this study, we used a reverse phenotyping approach to investigate the Liddle syndrome phenotypic spectrum and genotype–phenotype correlations. Methods Pubmed, Embase, Scopus, and the Human Gene Mutation Database were searched for articles reporting Liddle syndrome variants. The genetic variants were systematically classified to identify patients with genetically confirmed Liddle syndrome. We identified 62 articles describing 45 unique variants within 86 Liddle syndrome families, and phenotypic data were pooled for 268 patients with confirmed Liddle syndrome. Results The Liddle syndrome variants localized to exon 13 of SCNN1B and SCNN1G, disrupting the PPPxY motif critical for downregulating ENaC activity. Hypertension sensitive to ENaC inhibition was present in 97% of adults carrying Liddle syndrome variants while hypokalemia, metabolic alkalosis, and plasma renin and aldosterone suppression showed incomplete penetrance. In addition, 95% and 55% of patients had a family history of hypertension or cerebrovascular events, respectively. The genotype had minor phenotypic effects; however, probands compared with relatives showed significant phenotypic discrepancies consistent with selection bias for initial genetic screening. Conclusions Patients with genetically confirmed Liddle syndrome displayed a phenotypic spectrum, with ENaC-sensitive hypertension and family history of hypertension being the most common features. The phenotype seemed independent of the specific gene or variant type involved....

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基因证实的利德尔综合征患者的逆转表型

经基因证实的利德尔综合征的表型谱尚不清楚，一些患者可能仍未确诊并面临治疗无效的风险。在本研究中，我们使用反向表型分析方法来研究 Liddle 综合征表型谱和基因型-表型相关性。方法 在 Pubmed、Embase、Scopus 和人类基因突变数据库中搜索报告 Liddle 综合征变异的文章。对遗传变异进行系统分类，以识别经基因证实的利德尔综合征患者。我们鉴定了 62 篇文章，描述了 86 个 Liddle 综合征家族中的 45 种独特变异，并汇总了 268 名确诊 Liddle 综合征患者的表型数据。结果 Liddle 综合征变异体定位于 SCNN1B 和 SCNN1G 的外显子 13，破坏了对于下调 ENaC 活性至关重要的 PPPxY 基序。 97% 携带 Liddle 综合征变异体的成年人存在对 ENaC 抑制敏感的高血压，而低钾血症、代谢性碱中毒、血浆肾素和醛固酮抑制则显示不完全外显。此外，95%和55%的患者分别有高血压或脑血管事件家族史。基因型对表型的影响较小；然而，先证者与亲属相比表现出显着的表型差异，这与初始遗传筛查的选择偏差一致。结论 基因确诊的 Liddle 综合征患者表现出一定的表型谱，其中 ENaC 敏感性高血压和高血压家族史是最常见的特征。表型似乎与所涉及的特定基因或变异类型无关......