3例Gitelman综合征患者临床特点和基因突变分析及文献总结

目的 分析3例Gitelman综合征患者临床表型以及基因突变类型，总结Gitelman综合征的临床特点。 方法 收集2016年1月—2017年1月浙江大学医学院附属杭州市第一人民医院收治的3例Gitelman综合征患者的临床资料，并提取患者外周血单个核细胞基因组DNA，首先通过高通量测序法寻找与低钾血症相关的36个基因所有外显子的突变位点，再通过直接测序法对患者及其父母验证。同时在万方数据库和中国知网检索经过基因突变分析确诊的Gitelman综合征，比较不同基因突变型的血钾和血镁的差异。 结果 3例患者均表现为反复低钾血症、代谢性碱中毒、高肾素、正常血压，其中只有第2例有明显的低镁血症。基因测序结果显示病例1为SCL12A3基因复合杂合突变，病例2为SCL12A3基因纯合突变，病例3为SCL12A3杂合突变联合CLCNKB杂合突变。经检索共有79例临床资料完整的Gitelman综合征病例纳入分析，结果提示不同基因突变型之间血钾和血镁差异无统计学意义。移码和无意义突变与其他突变相比血钾和血镁差异无统计学意义。血镁降低组的血钾较血镁正常组偏低。 结论 Gitelman综合征临床表型多样，异质性明显，最终确诊仍需要基因突变分析。不同突变之间血钾和血镁差异无统计学意义，血镁降低者临床表型较重。 

Clinical features and genetic analysis of three patients with Gitelman syndrome and literature review

Objective To analyze the clinical phenotype and gene mutation types in 3 patients with Gitelman syndrome and summarize the clinical features of Gitelman syndrome. Methods The clinical data of 3 inpatients clinically diagnosed as Gitelman syndrome (GS) were collected. The genomic DNA was isolated from the peripheral blood and performed high throughput sequencing and bioinformatics analysis to analysis the all exons of 36 genes related with hypohalemia. Furthermore, Direct sequencing of PCR products in the mutation sites was performed in all patients and their parents. Meanwhile the Gitelman syndrome diagnosed by gene mutation analysis was searched in Wanfang database and China Knowledge Network to compare the differences of serum potassium and blood magnesium between different gene mutations. Results Three patients manifested with recurrent hypokalemia, metabolic alkalosis, but normal blood pressure. Gene sequencing results showed that compound heterozygous mutation of SCL12A3 in case 1 and homozygous mutation of SCL12A3 in case 2. Heterozygous mutation of SCL12A3 and CLCNKB were found in case 3. A total of 79 cases of Gitelman syndrome with complete clinical data were included in the analysis. The results showed that there was no significant difference in serum potassium and blood magnesium between different gene mutations. Conclusions Gitelman syndrome have diverse phenotype and the final diagnosis still requires genetic mutation analysis. There was no significant difference in serum potassium and blood magnesium between different gene mutations. The blood magnesium reduction group has a serious clinical phenotype