71例Gitelman综合征患者的临床和遗传学分析  

Clinical and genetic features of 71 patients with Gitelman syndrome

作　　者：吴婷 臧丽[2] 陈康[2] 裴育[2] 巴建明[2] 窦京涛[2] 吕朝晖[2] 母义明[2] 谷伟军[2] WU Ting;ZANG Li;CHEN Kang;PEI Yu;BA Jianming;DOU Jingtao;LYU Zhaohui;MU Yiming;GU Weijun(Chinese PLA Medical School,Beijing 100853,China;Department of Endocrinology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心内分泌科,北京100853

出　　处：《解放军医学院学报》2022年第5期579-585,共7页Academic Journal of Chinese PLA Medical School

基　　金：海南省自然科学基金面上项目(819MS112)。

摘　　要：背景Gitelman综合征(Gitelman syndrome,GS)是最常见的遗传性肾小管病变,临床表现多不典型,存在着很大的漏诊、误诊风险。我国对GS认识较晚,遗传性研究领域相对薄弱,缺乏大样本GS患者的基因型与表型相关性研究。目的探讨GS患者的临床和遗传特征,以提高对该病的认识和诊治。方法收集2007年7月-2020年9月于解放军总医院第一医学中心内分泌科就诊的71例临床诊断为GS患者的临床资料并进行基因分析,并进一步探讨基因型与表型的相关性。结果71例GS患者中,男性44例,女性27例。临床表现以神经肌肉系统受累相关表现为主,女性患者较男性患者更易出现肌肉痉挛或抽搐(40.7%vs 18.2%,P=0.037)和肢体麻木(37.0%vs 15.9%,P=0.043)。所有患者入院时均合并低钾血症,16例(22.5%)无低镁血症,6例(8.4%)无典型低尿钙。71例GS患者中3例未检测到SLC12A3基因突变,1例疑似多个基因缺失,其余67例患者检测出70种不同SLC12A3基因突变类型,其中25种为新发突变。p.D486N和p.T60M为最常见的突变类型,分别占28%(20/71)和11%(8/71)。纯合突变患者的血钾水平显著低于复合杂合突变患者(P=0.015)。结论GS患者基因型与表型异质性明显,部分患者血镁和尿钙水平正常,p.D486N和p.T60M为本研究中的热点突变。除SLC12A3基因外,还有其他遗传因素在GS病理过程中发挥作用。纯合突变患者的低钾血症相对较重。Background Gitelman syndrome(GS)is the most frequent inherited tubulopathy,with atypical clinical manifestations and great risk of missed diagnosis and misdiagnosis.We have a late understanding of GS and the field of genetic research is relatively weak.There are few large sample studies on the genotype-phenotype correlations of GS patients in China.Objective To investigate the clinical and genetic characteristics of GS,and improve the understanding,diagnosis and treatment of this disease.Methods Clinical data about 71 patients with diagnosed GS in the Department of Endocrinology of the First Medical Centre of Chinese PLA General Hospital from July 2007 to September 2020 were collected,and genetic analysis was conducted,then the correlation between genotype and phenotype was explored.Results Among the 71 GS patients,44 cases were male and 27 cases were female,and the neuromuscular system was most frequently involved in the clinical manifestations.Female patients were more likely to develop muscle cramps(40.7%vs 18.2%,P=0.037)and limb numbness(37.0%vs 15.9%,P=0.043).All patients presented with hypokalemia at admission,while hypomagnesemia and typical hypocalciuria were not found in 16(22.5%)and 6(8.4%)patients,respectively.SLC12A3 gene mutations were not detected in 3 patients,and multiple gene deletions were suspected in 1 patient,and 70 different SLC12A3 gene mutation types were detected in the remaining 67 patients,of which 25 were new mutations.p.D486N and p.T60M were the most common mutations,which were found in 20(28%)and 8(11%)patients,respectively.The serum potassium level of homozygous mutation patients was significantly lower than that of compound heterozygous mutation patients(P=0.015).Conclusion The genotype and phenotype of GS patients are obviously heterogeneous.Some patients have normal serum magnesium and urinary calcium levels.p.D486N and p.T60M are the hotspot mutations in this study.In addition to the SLC12A3 gene,there are other genetic factors that play roles in the pathological process of GS.H

关 键 词：GITELMAN综合征 基因型 表型 SLC12A3基因突变 遗传性肾小管病变 

分 类 号：R692.6[医药卫生—泌尿科学]