Zuo Jianxin, Guo Wencong, Wang Shujuan, Lang Yanhua, Wang Sai, Shi Xiaomeng, Zhang Ruixiao, Zhao Xiangzhong, Han Yue, Shao Leping
Department of Obstetrics, the Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China; Department of Nephrology, the Affiliated Qingdao Municipal Hospital of Qingdao University, No.5 Donghai Middle Road, Qingdao 266071, People's Republic of China.
Department of Nephrology, the Affiliated Qingdao Municipal Hospital of Qingdao University, No.5 Donghai Middle Road, Qingdao 266071, People's Republic of China; Department of Nephrology, the Affiliated Qingdao Municipal Hospital of Shandong University, No.5 Donghai Middle Road, Qingdao 266071, People's Republic of China; Central Laboratory, the Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China.
Clin Chim Acta. 2020 Dec;511:248-254. doi: 10.1016/j.cca.2020.10.002. Epub 2020 Oct 12.
Bartter syndrome type 2 (BS2) is an autosomal recessive renal tubular disorder, which is caused by the mutations in KCNJ1. This study was designed to analyze and describe the genotype and clinical features of five Chinese probands with BS2.
Identify KCNJ1 gene variants by the next generation sequencing and evaluate their mutation effects according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines.
Ten variants including eight novel ones of KCNJ1 gene were found, the most common type was missense variant. The common symptoms and signs 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). Two patients presented with hypochloremic metabolic alkalosis and hypokalemia; whereas the acid-base disturbance was absent in the others. One patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal PTH levels. All patients had nephrocalcinosis and/or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin has significant therapeutic effect on the growth retardation, polydipsia and polyuria and treatment was associated with a decrease in urine calcium excretion, normalization of electrolyte disturbance and PTH parameters.
Ten variants of KCNJ1 gene were identified in five Chinese probands. These patients had atypical BS phenotype lacking evident metabolic alkalosis and/or manifesting with PTH overaction/resistance, which reminds clinicians to carefully differentiate BS2 with other parathyroid disorders. This is the first report of BS2 from Chinese populations.
2型巴特综合征（BS2）是一种常染色体隐性遗传性肾小管疾病，由KCNJ1基因突变引起。本研究旨在分析并描述5例中国BS2先证者的基因型和临床特征。
采用二代测序技术鉴定KCNJ1基因变异，并根据2015年美国医学遗传学与基因组学学会（ACMG）标准和指南评估其突变效应。
共发现10种KCNJ1基因变异，其中8种为新变异，最常见的类型为错义变异。常见症状和体征的发生率由高到低依次为：烦渴和多尿（5/5），其中1例（1/5）表现为尿崩症；母亲羊水过多和早产（4/5）；生长发育迟缓（3/5）。2例患者出现低氯性代谢性碱中毒和低钾血症，其余患者无酸碱平衡紊乱。1例患者有明显的甲状旁腺激素（PTH）抵抗（低钙血症、高磷血症和PTH水平显著升高），3例表现为PTH作用亢进（高钙血症、低磷血症和PTH水平轻度升高），1例血钙和血磷浓度正常，PTH水平略高于正常。所有患者均有肾钙质沉着症和/或高钙尿症，其中1例并发肾结石。吲哚美辛对生长发育迟缓、烦渴和多尿有显著治疗效果，治疗后尿钙排泄减少，电解质紊乱和PTH参数恢复正常。
在5例中国先证者中鉴定出10种KCNJ1基因变异。这些患者具有非典型的BS表型，缺乏明显的代谢性碱中毒和/或表现为PTH作用亢进/抵抗，提醒临床医生需仔细鉴别BS2与其他甲状旁腺疾病。这是中国人群中关于BS2的首次报道。
