Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes among individuals with hypertension and hypokalemia.

PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.