Premature Stroke Secondary to Severe Hypertension Results from Liddle Syndrome Caused by a Novel SCNN1B Mutation
Premature Stroke Secondary to Severe Hypertension Results from Liddle Syndrome Caused by a Novel SCNN1B Mutation
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DOI：
10.1159/000507580
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发表时间：
2020-07-01
影响因子：
2.8
通讯作者：
Zhou, Xian-Liang
中科院分区：
文献类型：
--
作者：
Fan, Peng;Zhang, Di;Zhou, Xian-Liang
简介：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cnn1a、SCNN1B和scnn1g的致病性突变引起。目的：本研究旨在从一个有中风病史的中国家庭中鉴定一个新颖的scnn1bmissense突变，并证实该突变与该家庭的LS有关。方法：先证者及另外11名亲属采集DNA样本。在先证者中进行下一代测序以寻找候选变体。为了排除遗传多态性，通过Sanger测序在其他家族成员、100名高血压患者和100名健康对照中验证了候选变异scnn1b。结果：基因检测在先证者中发现了一种新的、罕见的scnn1杂合变异。该变异导致在密码子617处的苏氨酸取代脯氨酸，改变了β - enac的PY基序。所鉴定的突变仅在5个亲属中得到证实。计算机分析表明该变异具有高致病性。在这个家族中，6例LS患者存在表型异质性。阿米洛利个体化用药可有效控制LS患者高血压，改善患者血清钾浓度。结论：我们在一个LS患者家庭中发现了一个新的scnn1b突变（c.1849C> a）。LS患者，尤其是重度高血压患者，应警惕早发卒中的发生。通过基因检测及时诊断和阿米洛利量身定制的治疗可以帮助LS患者避免严重的并发症。
Introduction:Liddle syndrome (LS), an autosomal dominant and inherited monogenic hypertension syndrome caused by pathogenic mutations in the epithelial sodium channel (ENaC) genesSCNN1A,SCNN1B, andSCNN1G.Objective:This study was designed to identify a novelSCNN1Bmissense mutation in a Chinese family with a history of stroke, and to confirm that the identified mutation is responsible for LS in this family.Methods: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 variantinSCNN1Bwas verified in other family members, 100 hypertensives, and 100 healthy controls by Sanger sequencing.Results:Genetic testing revealeda novel and rare heterozygous variant inSCNN1Bin the proband. This variant resulted in a substitution of threonine instead of proline at codon 617, altering the PY motif of beta-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.Conclusions:We identified a novelSCNN1Bmutation (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.