Mutation analysis of <italic>KCNJ1</italic> gene and investigation of phenotype in 5 Chinese patients with Bartter syndrome type 2

Yue Han; Yanhua Lang; Shujiao Xiao; Xiaomeng Shi; Sai Wang; Ruixiao Zhang; Wencong Guo; Xiangzhong Zhao; Leping Shao

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Mutation analysis of KCNJ1 gene and investigation of phenotype in 5 Chinese patients with Bartter syndrome type 2

VernacularTitle: 中国5例2型巴特综合征KCNJ1基因变异分析和临床表型研究
Author: Yue HAN ¹ ; Yanhua LANG ² ; Shujiao XIAO ² ; Xiaomeng SHI ¹ ; Sai WANG ¹ ; Ruixiao ZHANG ¹ ; Wencong GUO ¹ ; Xiangzhong ZHAO ³ ; Leping SHAO ¹
Author Information

1. Department of Nephrology, the Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao 266071, China
2. Department of Nursing, the Affiliated Hospital of Qingdao University, Qingdao 266003, China
3. Central Laboratory, the Affiliated Hospital of Qingdao University, Qingdao 266071, China
Publication Type:Clinical Trail
Keywords: Bartter syndrome; Genotype; Phenotype; KCNJ1 gene
From: Chinese Journal of Nephrology 2020;36(2):115-122
CountryChina
Language:Chinese
Abstract: Objective:To identify and analyze the variants of the KCNJ1 gene in five Chinese patients with Bartter syndrome type 2 (BS2), and to describe their clinical features as well as treatment results.
Methods:Data and blood samples of five BS2 patients and their relatives confirmed by Qingdao Municipal Hospital from June 2012 to January 2019 were collected. Whole-exome-sequencing (WES) based on the second generation high throughput sequencing was performed to detect variants. The 2015 American College of Medical Genetics and Genomics Standards and Guidelines were applied to analyze the pathogenicity of the variants. The clinical features and laboratory results were retrospectively studied. The response to treatment and follow-up data were reviewed.
Results:Ten variants including six novel ones of KCNJ1 gene were identified through WES and verified by Sanger dideoxy sequencing. Missense variants accounted for the highest proportion. The common symptoms and signs of five BS2 patients from high to low incidence were polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Initially, two patients presented with hypochloremic metabolic alkalosis and hypokalemia, whereas the acid-base disturbance was absent in the others. One patient experienced hyperkalemia. In terms of calcium-phosphorus metabolism, one patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated serum intact PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated serum intact PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal serum intact PTH levels. All patients had nephrocalcinosis or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin helped to correct the growth retardation, halt polydipsia polyuria, decrease the elevated urinary calcium excretion, and normalize electrolyte disturbance as well as PTH parameters in some patients.
Conclusions:This investigation identifies ten variants of KCNJ1 gene, including six ones that have not been previously reported, which will enrich the human gene mutation database (HGMD). These patients in our study have atypical BS phenotype, so that careful differentiation from other parathyroid diseases will be required for clinicians.