中国人Gitelman综合征高发突变的基因型和表型特征  

Characteristic of genotype-phenotype in Chinese patients with high frequency variant of Gitelman syndrome

作　　者：秦岭[1] 邵乐平[1] 任红[1] 王伟铭[1] 张文[1] 陈楠[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,上海200025

出　　处：《肾脏病与透析肾移植杂志》2008年第4期331-334,共4页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：上海市卫生局重点学科基金(05III001);上海市重点学科(T0201);上海市卫生局重点课题(2003ZD002);国家自然科学基金(30670972)

摘　　要：目的:Gitelman综合征(GS)是由于SLC12A3基因的突变导致遗传性肾小管病。我们对28例临床诊断GS患者进行了基因诊断,旨在探讨中国人GS的基因型和表型有无联系。方法:对28例GS患者抽取外周血测DNA,对GS的致病基因SLC12A3和经典型Bartter综合征的致病基因CLCNKB测序,分析经基因确诊GS患者的临床表现以及血、尿、电解质、血pH、血管紧张素、血醛固酮、血压等水平,寻找中国人GS基因型和表型的关系。结果:28例患者均发现SLC12A3的突变,其中14例携带T60M,4例为纯合T60M突变,10例为杂合T60M突变,突变频率高达33%。T60M携带者的发病年龄、生长发育障碍、四肢乏力等症状的发生与携带其他突变的患者相比无显著差异。T60M携带者血碳酸氢根离子明显高于带其他突变的患者,尿钾排泄分数明显高于其他突变类型的患者;两组间在血钾、血氯、血镁、血管紧张素、血醛固酮、尿pH、24h尿钾、尿氯离子相比较均无统计学差异。结论:T60M突变是中国人GS的高频突变。目前尚无直接证据支持T60M与GS的表型有明确的关系。Objective：Gitelman syndrome （GS） is an autosomal recessive renal tubulopathy, which is caused by the inactivating mutations in the SLC12A3 gene. The aim of this paper was to explore the characteristic of genotype and phenotype in Chinese patients with high frequency variant of Gitelman syndrome. Methodology：The genomie DNA was isolated from the peripheral blood and the primers were designed to amplify all 26 exons in the SLC12A3 gene and 19 exons in the CLCNKB gene by PCR. Direct sequencing of PCR products in the SLC12A3 gene and CLCNKB gene was performed in all patients to diagnose Gitelman syndrome. The clinical features and biochemical parameters were compared and ana- lyzed to explore the characteristic of genotype and phenotype in Chinese GS patients with high frequency variant. Results ： Variants in the SLC12A3 gene were detected in all patients. 14 of them carried the variant Thr60 Met （T60 M） , 4 of whom were homozygous and 10 were heterozygous. The frequency of T60 M was up to 33%. There were no differences in onset age, main complains between T60 M group and other variant group. The level of serum bicarbonate and urinary fraction excretion of potassium were higher in T60 M group than that in other type variant group [ （30. 0 ±1.20） mmol/L versus （28.8±1.52） mmol/L; （35.0 ±25.8）% versus （ 19.6±6. 02）% ]. There were no statistical differences in other biochemical parameters between T60M group and other variant group. No variants in the CLCNKB gene were detected. Conclusion：Thr60 Met in SLC12A3 gene is a high frequency variant in Chinese patients with Gitelman syndrome. There is no enough evidence of showing definite correlation between Thr60Met and phenotype.

关 键 词：GITELMAN综合征 基因型 表型 突变 

分 类 号：R692.6[医药卫生—泌尿科学]