Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Emergency and Critical Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Kidney Blood Press Res. 2020;45(4):603-611. doi: 10.1159/000507580. Epub 2020 Jul 22.
Liddle syndrome (LS), an autosomal dominant and inherited monogenic hypertension syndrome caused by pathogenic mutations in the epithelial sodium channel (ENaC) genes SCNN1A, SCNN1B, and SCNN1G.
This study was designed to identify a novel SCNN1B missense mutation in a Chinese family with a history of stroke, and to confirm that the identified mutation is responsible for LS in this family.
DNA samples were collected from the proband and 11 additional relatives. Next-generation sequencing was performed in the proband to find candidate variants. In order to exclude genetic polymorphism, the candidate variantin SCNN1B was verified in other family members, 100 hypertensives, and 100 healthy controls by Sanger sequencing.
Genetic testing revealeda novel and rare heterozygous variant in SCNN1B in the proband. This variant resulted in a substitution of threonine instead of proline at codon 617, altering the PY motif of β-ENaC. The identified mutation was only verified in 5 relatives. In silico analyses indicated that this variant was highly pathogenic. In this family, phenotypic heterogeneity was present among 6 LS patients. Tailored medicine with amiloride was effective in controlling hypertension and improving the serum potassium concentration in patients with LS.
We identified a novel SCNN1B mutation (c.1849C>A) in a family affected by LS. Patients with LS, especially those with severe hypertension, should be alert for the occurrence of premature stroke. Timely diagnosis using genetic testing and tailored treatment with amiloride can help LS patients to avoid severe complications.
Liddle 综合征（LS）是一种常染色体显性遗传性单基因高血压综合征，由上皮钠通道（ENaC）基因 SCNN1A、SCNN1B 和 SCNN1G 的致病变异引起。
本研究旨在鉴定一个中国有中风家族史的 LS 家系中的新型 SCNN1B 错义突变，并证实该突变是该家系中 LS 的致病原因。
收集先证者及其 11 位其他亲属的 DNA 样本。在先证者中进行下一代测序以寻找候选变异。为了排除遗传多态性，通过 Sanger 测序在其他家庭成员、100 名高血压患者和 100 名健康对照中验证候选变异 SCNN1B。
基因检测显示先证者中 SCNN1B 存在一种新型且罕见的杂合变异。该变异导致第 617 密码子的苏氨酸被脯氨酸取代，改变了 β-ENaC 的 PY 基序。该突变仅在 5 位亲属中得到验证。计算机分析表明该变异具有高度致病性。在这个家系中，6 位 LS 患者存在表型异质性。用阿米洛利进行个体化治疗对控制高血压和改善 LS 患者的血清钾浓度有效。
我们在一个受 LS 影响的家系中鉴定出一种新型的 SCNN1B 突变（c.1849C>A）。LS 患者，尤其是那些有严重高血压的患者，应警惕过早发生中风。通过基因检测及时诊断和使用阿米洛利进行个体化治疗有助于 LS 患者避免严重并发症。
