A novel compound heterozygous mutation of SLC12A3 gene in a pedigree with Gitelman syndrome and literature review
A novel compound heterozygous mutation of SLC12A3 gene in a pedigree with Gitelman syndrome and literature review
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Gitelman综合征家系SLC12A3基因新型复合杂合突变及文献复习
DOI：
10.1007/s13258-020-00960-6
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发表时间：
2020-07
期刊：
影响因子：
2.1
通讯作者：
Yaomin Hu
中科院分区：
文献类型：
--
作者：
Minglan Yang;Ying Dong;Jianqing Tian;Li Yan;Yawen Chen;Huiying Qiu;Wei Liu;Yaomin Hu
dgitelman综合征（GS）是一种由slc12a3基因突变引起的以低钾血症、低镁血症、低钙尿症和代谢性碱中毒为特征的小管病。目的对1例GS家系slc12a3基因突变进行研究，分析其临床表现。方法采用新一代测序和Sanger测序方法，对1例59岁男性GS患者和3代内11名家族成员的GS家系slc12a3基因突变进行分析。结果在先证者中发现一个新的slc12a3基因复合杂合突变（第14外显子C . 1712t > C和第26外显子C .2986_2987ins GCT）。此外，我们证明了两个兄弟与先证者共享相同的杂合突变，但只有一个兄弟有GS相关症状。他的侄子是一种突变的携带者（C . 1712t > C），他的一个兄弟，他的妹妹和侄女是另一种突变的携带者（C .2986_2987in GCT）。结论在GS中首次发现新的致病化合物slc12a3基因杂合突变。我们的结果进一步支持在GS中缺乏表型-基因型相关性。GS的病理生理机制有待进一步的功能研究。
BackgroundGitelman syndrome (GS) is a tubulopathy characterized by hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis, which is caused by mutations inSLC12A3gene.ObjectiveThe objective of this study was to investigate the mutation ofSLC12A3gene in a pedigree with GS and analyzed the clinical manifestations.MethodsNext-generation sequencing and Sanger sequencing were performed to explore the mutations ofSLC12A3gene in a GS pedigree that included a 59-year-old male GS patient and a total of 11 family members within three generations.ResultsA novel compound heterozygous mutation ofSLC12A3gene (c.1712T > C in exon14 and c.2986_2987ins GCT in exon26) was identified by genetic testing in the proband. Moreover, we demonstrated that two brothers shared the same heterozygous mutation with the proband, but only one brother had the GS related symptoms. His nephew was the carrier of one mutation (c.1712T > C), and one of his brother, his sister and niece were carriers of the other (c.2986_2987ins GCT).ConclusionsThis is the first study to report the novel pathogenic compound heterozygous mutation ofSLC12A3gene in GS. Our result further supports the lack of phenotype–genotype correlations in GS. Further functional studies are required to investigate pathophysiologic mechanisms of GS.
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通讯作者：
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