10例Gitelman综合征患者SLC12A3基因的检测

Analysis of Sl Cl2A3 gene mutation in patients with Gitelman syndrome

目的:对青岛地区10例可疑Gitelman综合征患者致病基因SLC12A3和CLCNKB的突变特点进行分析。方法:通过直接测序的方法进行突变分析。选取100例健康人作为对照。结果:共确定SLC12A3基因9个突变位点,其中3个为新突变位点,包括2个错义突变:Glu429Lys,Ala264Gly;1个缺失突变:1740del C。6个已报道过的突变,其中包括5个错义突变:Cys430Gly,Asp486Asn,Ser283Tyr,Thr163Met,Arg913Gln;1个缺失突变:2877_2878del AC。10例患者中8例携带Ala264Gly纯合突变,4例携带Asp486Asn杂合突变,大部分患者为复合杂合突变。结论:本研究共发现9个突变位点,其中3个新突变位点。

Objective： To identify the new mutations of SLCl2A3 and CLCNKB gene in patients with suspicious Gitelman syndrome,and Analyze the characteristics of the genetic mutations. Methodology： Ten patients hospitalized in the affiliated hospital of Qingdao university with the clinical and biochemical features of Gitelman syndrome were analyzed by direct sequencing of SLCl2A3 gene. One hundred unrelated normal subjects were selected to evaluate all the mutations found by this study and make sure that they are new mutations through the Human Gene Mutation date base. Results： Nine mutations were identified in SLCl2A3 gene of 10 patients with Gitelman syndrome. Four were novel variants,including 2missense mutations： Glu429 Lys,Ala264Gly,and one deletions： 1740 del C. Six were recurrent ones including 5 missense mutations： Cys430 Gly,Asp486Asn,Ser283 Tyr,Thr163Met,Arg913Gln; and one deletion： 2877_ 2878 del AC. The Homozygous mutation Ala264 Gly was found in 8 of 10 patients while the heterozygous mutation Asp486 Asn in 4 of 10. The majority of the patients were compound heterozygous. Conclusion： Nine mutations were identified in SLCl2A3 gene of 10 patients with Gitelman syndrome,and 3 were novel variants.