摘要
目的分析Gitelman综合征患者的临床特征及基因突变类型。方法收集先证者及家系成员临床资料及实验室检查结果,采集其外周静脉血,经测序分析寻找相关突变位点,结合临床特征对其突变基因进行分析。结果先证者的临床特征和实验室检查基本符合Gitelman综合征诊断。基因突变分析显示,先证者及其弟弟的SLC12A3基因第1号外显子存在c.248G>A(p.Arg83Gln)杂合错义的致病突变;先证者、先证者弟弟和先证者女儿的SLC12A3基因第7号内含子与第8号外显子之间存在c.965-1_976delins-ACCGAAAATTTT缺失插入突变,该突变可导致NCCT蛋白在第7内含子和第8外显子之间的剪接位点异常,最终导致蛋白活性和功能受损。结论Gitelman综合征患者起病隐匿,临床医师需详细问诊与完善实验室检验;SLC12A3基因c.248G>A(p.Arg83Gln)和c.965-1_976delins-ACCG A A AATTTT突变是该Gitelman综合征家系的可能致病变异。
Objective This paper aims to analyze the clinical characteristics and gene mutation types of patients with Gitelman syndrome.Methods The clinical data and laboratory examination results of the proband and family members were collected,and their peripheral venous blood was collected.The relevant mutation sites were found by sequencing analysis,and the mutant genes were analyzed combined with clinical characteristics.Results The clinical features and laboratory examination of the proband are basically consistent with the diagnosis of Gitelman syndrome.Gene mutation analysis showed that there was a c.248G>A(p.Arg83Gln)heterozygous missense mutation on exon 1 of SLC12A3 gene of the proband and his younger brother.There is a c.965-1_976delins-ACCGAAAATTTT deletion insertion mutation between intron 7 and exon 8 of SLC12A3 gene in the proband,brothers and daughters of the proband,which can lead to abnormal splicing site of NCCT protein between intron 7 and exon 8,resulting in the damage of protein activity and function.Conclusion The onset of Gitelman syndrome is hidden,clinicians need detailed consultation and laboratory examination,SLC12A3 gene c.248G>A(p.Arg83Gln)and c.965-1_976delins-ACCGAAAATTTT mutations are the possible pathogenic variants of this pedigree with Gitelman syndrome.
作者
蔡晓晓
童郁
陈璐
施建有
CAI Xiao-xiao;TONG Yu;CHEN Lu;SHI Jian-you(Clinical Laboratory,Wenzhou People's Hospital,Zhejiang 325800,China)
出处
《中国卫生检验杂志》
CAS
2023年第11期1351-1353,共3页
Chinese Journal of Health Laboratory Technology
基金
温州市科技计划项目(Y2020580)。
