Abstract
Background
Gitelman syndrome (GS) is a tubulopathy characterized by hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis, which is caused by mutations in SLC12A3 gene.
Objective
The objective of this study was to investigate the mutation of SLC12A3 gene in a pedigree with GS and analyzed the clinical manifestations.
Methods
Next-generation sequencing and Sanger sequencing were performed to explore the mutations of SLC12A3 gene in a GS pedigree that included a 59-year-old male GS patient and a total of 11 family members within three generations.
Results
A novel compound heterozygous mutation of SLC12A3 gene (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).
Conclusions
This is the first study to report the novel pathogenic compound heterozygous mutation of SLC12A3 gene 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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Acknowledgments
This study was supported by the National Natural Scientific Foundation of China (nos. 81870554, 81800747), which were mainly for the collection, genetic analysis, and interpretation of data.
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YD was the chief physician for this patient. ML Y and JQ T were the attending physicians for this patient and also collected the data of this pedigree. ML Y drafted the manuscript. LY, YW C and HY Q helped to collect the blood samples from the pedigree. WL and YM H diagnosed the disease and reviewed the manuscript. All authors have read and approved the manuscript in its final version prior to submission.
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Minglan Yang,Ying Dong, Jianqing Tian, Li Yan, Yawen Chen, Huiying Qiu, Wei Liu and Yaomin Hu declare that they have no conflict of interest.
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Yang, M., Dong, Y., Tian, J. et al. A novel compound heterozygous mutation of SLC12A3 gene in a pedigree with Gitelman syndrome and literature review. Genes Genom 42, 1035–1040 (2020). https://doi.org/10.1007/s13258-020-00960-6
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DOI: https://doi.org/10.1007/s13258-020-00960-6