Two patients with Gitelman syndrome were admitted to the Department of Endocrinology, Third Xiangya Hospital of Central South University. The genomic DNA from the patients' peripheral blood was extracted and the whole-exome sequencing was performed to detect the possible mutations. The function of the mutation sites was analyzed by bioinformatics software. Through whole-exome sequencing and Sanger sequencing, we have found that 2 patients with Gitelman syndrome carried compound heterozygous mutations of SLC12A3 gene, which were c.486_490delTACGGinsA, p.R943W, p.D486N, and p.R928C. Among them, c.486_490delTACGGinsA insertion deletion mutation causes frame shift and protein truncation. The p.R943W, p.D486N, and p.R928C of SLC12A3 gene were predicted to be pathogenic mutations by SIFT, PolyPhen2, and Mutation Taster. These 4 mutations were all reported, but p.R943W was first reported in Chinese population. Gitelman syndrome is rare in clinic and the rate of missed diagnosis is high. Early genetic analysis in patients with Gitelman syndrome is helpful to determine the etiology and guide the treatment.
中南大学湘雅三医院内分泌科收治了2例疑诊Gitelman 综合征的患者。抽取2例患者外周血进行基因组DNA抽提，然后采用全外显子组测序进行基因学检测，寻找致病位点，并通过生物信息学软件对突变位点进行功能分析。全外显子组测序及Sanger测序验证发现2例Gitelman 综合征患者均携带SLC12A3基因复合杂合突变：c.486_490delTACGGinsA、p.R943W、p.D486N及p.R928C。其中c.486_490delTACGGinsA插入缺失突变将造成框移及蛋白质截短，而p.R943W、p.D486N及p.R928C突变经SIFT、PolyPhen2和Mutation Taster预测为有害。这4个突变既往均有报道，其中p.R943W为首次在中国人群中发现。Gitelman综合征临床较罕见，漏诊率高。对Gitelman 综合征患者及早进行基因检测有助于明确病因及指导治疗。.
Keywords: Gitelman syndrome; SLC12A3; hypokalemia; whole-exome sequencing.