摘要
目的分析Gitelman综合征(Gitelman syndrome,GS)患者临床表现特点和基因突变类型。方法在分析10例GS患者临床表现和实验室相关检查结果的基础上,对其进行GS致病基因--SLC12A3基因突变位点的检测。首先在获得患者知情同意书后抽取其外周血提取基因组DNA,然后通过聚合酶链式反应(polymerase chain reaction,PCR)扩增目的基因的26个外显子及其侧翼序列,最后采用sanger测序结合DNassist序列比对软件进行序列分析来确定突变位点。结果本研究共检测出13种致病突变,没有出现明显的热点突变位点,其中错义突变8种(61.5%),缺失突变3种(23.1%),内含子剪接位点突变2种(15.4%)。10例临床疑似患者中5例为复合杂合致病,占比50%;2例为纯合致病,占比20%;其余3例仅检出一处杂合致病突变位点。结论本研究检测到新的突变位点D62G、C146Y,其致病性未见相关文献报道,除此之外,本研究还发现GS临床表现与基因型之间并没有非常明确的关系,故临床上目前还不能通过基因型来判断患者疾病的严重程度和发展趋势。但是,基因诊断仍然是该病诊断的金标准,它除了可以确诊疾病,还可以实现疾病的早期筛查和产前的优生优育。
Objective To analyze the clinical features and gene mutations of Gitelman syndrome.Methods Based on the clinical symptoms and laboratory test results,this study analyzed the mutations of disease-causing gene SLC12A3 in 10 patients with Gitelman syndrome.After getting the informed consent of patients, the genomic DNA of peripheral blood was extracted.The 26 exons and their flanking sequences of SLC12A3 were amplified by polymerase chain reaction(PCR).Sanger sequencing was combined with DNassist sequence alignment software to confirm the mutations.Results In this study, we found 13 kinds of pathogenic mutations altogether.There was no hot spot mutation.There were eight kinds of missense mutations(61.5%), three kinds of deletion mutations(23.1%), and two kinds of splicesite mutations(15.4%).Among the ten clinical suspected patients, five cases were caused by compound heterozygous mutation, accounting for 50%.Two cases were homozygous mutation, accounting for 20%.Only one heterozygous pathogenic mutation was detected in the rest of patients.Conclusion In this study,two new mutation sites, D62 G and C146 Y, were founded, and their pathogenicity has not been reported.Beyond that,we found the relationship between phenotype and genotype was not clear.So we can?t estimate the severity and advancing of the disease according to the genotype.However, genetic diagnosis is also the gold standard for this disease.In addition to diagnose disease, it can also achieve early screening and prenatal diagnosis.
作者
路荣梅
李锦新
李连涛
陈刚
温俊平
LU Rongmei;LI Jinxin;LI Liantao;CHEN Gang;WEN Junping(Department of Endocrinology,Fujian Provincial Hospital,Fuzhou,Fujian 350001,China)
出处
《福建医药杂志》
CAS
2020年第2期24-29,共6页
Fujian Medical Journal
基金
福建省卫生计生委青年课题(2017/1/4)。
