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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Medical Genetics 1/2018

A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome pedigree

BMC Medical Genetics > Ausgabe 1/2018
Yixin Chen, Ziyi Zhang, Xihua Lin, Qianqian Pan, Fenping Zheng, Hong Li
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12881-018-0527-7) contains supplementary material, which is available to authorized users.



Gitelman syndrome (GS) is an autosomal recessive disorder caused by genic mutations of SLC12A3 (Solute carrier family 12 member 3), which encodes the Na-Cl cotransporter (NCC), and presents with characteristic metabolic abnormalities, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this study, we report a case of a GS pedigree, including analysis of GS-associated gene mutations.


We performed next-generation sequencing analysis and Sanger sequencing to explore the SLC12A3 mutations in a GS pedigree that included a 35-year-old female patient with GS and five family members within three generations. Furthermore, we summarized their clinical manifestations and analyzed laboratory parameters related to GS.


The female proband (the patient with GS) presented with intermittent fatigue and transient periods of tetany, along with significant hypokalemia, hypomagnesemia, and hypocalciuria. All other members of the pedigree had normal laboratory results without obvious GS-related symptoms. Genetic analysis of the SLC12A3 gene identified two novel missense mutations (c.1919A > G, p.N640S in exon 15; c.2522A > G, p.D841G in exon 21) in the patient with GS. Moreover, we demonstrated that her mother, younger maternal uncle, and cousin were carriers of one mutation (c.1919A > G), and her father was the carrier of the other (c.2522A > G).


This is the first report of these two novel pathogenic variants of SLC12A3 and their contribution to GS. Further functional studies are particularly warranted to explore the underlying molecular mechanisms.
Additional file 1: Table S1. Clinical and biochemical characteristics of all five family members. Clinical and biochemical characteristics of all five family members are listed in Table S1. (DOCX 14 kb)
Additional file 2: Table S2. Primer sequences of the SLC12A3 gene and annealing temperature of each pair. Thirty-three primer pairs designed to amplify the coding sequence of the SLC12A3 gene, and annealing temperature of each pair, are provided in Table S2. (DOCX 14 kb)
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