Gitelman综合征分子遗传学研究进展

Research process in molecular genetics of Gitelman syndrome

Gitelman综合征是由位于染色体16q13的SLC12A3基因突变引起的常染色体隐性遗传病,患病率为1~10∶40000,SLC12A3基因编码噻嗪类敏感的钠氯共同转运体(sodium-chloride cotransporters,NCC),介导Na+和Cl-的重吸收。该综合征以低钾性碱中毒、低镁血症和低尿钙为特征,基因型与表型之间有一定的相关性。在之前的研究中,已经发现了超过500种基因突变,并对其中的一些突变进行了功能学分析。本文综述了Gitelman综合征相关的基因突变和功能学研究,对其基因型和表型的关系进行了分析,总结了Gitelman综合征的分子遗传学研究进展。

Gitelman syndrome(GS)is an autosomal recessive genetic disease caused by mutations in the SLC12A3 gene located in chromosome 16q13.The incidence of GS is 1-10∶40000.SLC12A3 encodes thiazide-sensitive sodium-chloride cotransporters(NCC)which play key roles in Na+and Cl-reabsorption.GS is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesaemia and low urinary calcium excretion.There are some correlations between genotypes and phenotypes.In previous studies,more than 500 mutations have been identified and some of them have been functionally analyzed.We review genetic mutations and functional studies related to GS as well as the relationship between genotypes and phenotypes,and summarize the research process in molecular genetics of GS.