摘要目的:探讨2例Gitelman综合征(GS)患者的遗传学病因。方法:选取分别于2022年1月和6月就诊于临沂市人民医院的2例GS患者作为研究对象进行回顾性研究。收集患者的血清检测血清电解质水平及电解质排泄量资料。采集患者外周血样提取基因组DNA进行全外显子组测序，并进行Sanger测序验证。结果:患者1为27岁女性，血清钠、钾、氯及镁水平以及24 h尿氯、钙水平均低于参考值。基因检测发现其携带 SLC12A3: c．1456G>A(p.D486N)和 SLC12A3: c．179C>T(p.T60M)复合杂合变异，前者遗传自其母亲，为已报道致病性变异。患者2为4岁男性，血钠、氯和镁水平低于参考值，血钾出现危急值。 SLC12A3基因检出母源致病性c.602-16G>A和父源c.805_806insTTGGCGTGGTCTCGGTCA(p.V268_T 269insIGVVSV)复合杂合变异。根据美国医学遗传学与基因组学学会指南，患者2携带的变异均被判定为致病性变异(PVS1＋PM2_Supporting＋PP3；PVS1＋PM2_Supporting＋PM4)。 结论:上述 SLC12A3变异考虑为2例GS患者的遗传学病因。

abstractsObjective:To explore the genetic etiology of two patients with Gitelman syndrome (GS).Methods:Two patients who had presented at the Linyi People′s Hospital in January and June 2022 respectively were selected as the study subjects. Peripheral blood samples of them were collected and subjected to whole exome sequencing (WES). Electrolyte levels in their serum and urine were detected. Candidate variants were verified by Sanger sequencing. PyMOL software was used to predict the impact of the variants on the protein structure.Results:Patient 1 was a 27-year-old female with decreased serum levels of sodium, potassium, chloride and magnesium, along with decreased urine chloride and calcium. WES revealed that she has harbored compound heterozygous variants of the SLC12A3 gene, namely c. 1456G>A (p.D486N) and c. 179C>T (p.T60M). The former was inherited from her mother and known to be pathogenic. Patient 2 was a 4-year-old male with lower serum sodium, chloride and magnesium levels, and his serum potassium level was found to be critically low. He was found to harbor compound heterozygous variants of c. 602-16G>A and c. 805_806insTTGGCGTGGTCTCGGTCA (p.V268_T269insIGVVSV) of the SLC12A3 gene, which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PP3; PVS1+ PM2_Supporting+ PM4). Conclusion:The above heterozygous variants of the SLC12A3 gene probably underlay the GS in these patients.