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Background  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.    Methods  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.    Results  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).    Conclusion  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.    Electronic supplementary material  The online version of this article (10.1186/s12881-018-0527-7) contains supplementary material, which is available to authorized users.

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