a Department of Cardiology, Chaoyang Hospital , Capital Medical University , Beijing , China.
b Hypertension Center of Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Clin Exp Hypertens. 2019;41(4):381-388. doi: 10.1080/10641963.2018.1489547. Epub 2018 Jun 28.
Bartter syndrome (BS) and Gitelman syndrome (GS) are hereditary diseases characterized by hypokalemia with decreased or normal blood pressure (BP). However, BS or GS patients who present with elevated BP levels have been increasingly reported recently. Therefore, this study aimed to investigate the presence of BS and GS among individuals with unexplained hypokalemia with hypertension in a clinical setting.
Patients presented with unexplained hypertension and hypokalemia admitted to Hypertension Center of Fuwai Hospital from November 2015 to February 2017 were enrolled. High-throughput sequencing for five BS and GS causative genes were performed. Variants were classified using American College of Medical Genetics (ACMG) consensus guidelines.
Thirty-four patients with unexplained hypertension and hypokalemia were included for genetic analysis. A total number of 10 rare variants were identified in six individuals (mutation detection rate, 17.65%). One homozygous variant carried by one of the 34 patients, KCNJ1 c.941A> G (p.Tyr314Cys), were categorized as likely pathogenic variant and resulted in a diagnostic yield of 2.94%. Eight of the remaining nine variants were predicted to be deleterious by ≥ three bioinformatics software and may give additional potential diagnostic yields.
This is the first study performing combined genetic screening for BS and GS pathogenic genes among individuals with unexplained hypertension and hypokalemia. Our data suggested that BS or GS may contribute to the etiology of patients presented with hypertension and hypokalemia. Genetic testing for BS and GS pathogenic genes are recommended to facilitate precision diagnoses and targeted treatment.
巴特综合征（BS）和吉特曼综合征（GS）是遗传性疾病，其特征为低钾血症伴血压降低或正常。然而，最近越来越多报道称 BS 或 GS 患者伴有血压升高。因此，本研究旨在调查临床中不明原因低钾血症伴高血压患者中 BS 和 GS 的存在情况。
本研究纳入 2015 年 11 月至 2017 年 2 月期间因不明原因高血压和低钾血症就诊于阜外医院高血压中心的患者。对 5 个 BS 和 GS 致病基因进行高通量测序。根据美国医学遗传学学院（ACMG）共识指南对变异进行分类。
对 34 例不明原因高血压伴低钾血症患者进行了基因分析。在 6 例患者中发现了 10 个罕见变异（检出率为 17.65%）。34 例患者中的 1 例携带纯合变异 KCNJ1 c.941A>G（p.Tyr314Cys），被归类为可能致病性变异，诊断率为 2.94%。其余 9 个变异中的 8 个被≥3 种生物信息学软件预测为有害性变异，可能会提供额外的潜在诊断率。
这是第一项对不明原因高血压伴低钾血症患者进行 BS 和 GS 致病基因联合遗传筛查的研究。我们的数据表明，BS 或 GS 可能导致高血压伴低钾血症患者的发病。建议对 BS 和 GS 致病基因进行遗传检测，以促进精准诊断和靶向治疗。
