A novel compound heterozygous mutation of SLC12A3 gene in a pedigree with Gitelman syndrome and literature review

Background Gitelman syndrome (GS) is a tubulopathy characterized by hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis, which is caused by mutations inSLC12A3gene. Objective The objective of this study was to investigate the mutation ofSLC12A3gene in a pedigree with GS and analyzed the clinical manifestations. Methods Next-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. Results A 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). Conclusions This 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.