Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature

Objective Gitelman syndrome (GS) is one of the most common causes of inherited hypokalaemia. As it was caused by mutations in the SLC12A3 gene, GS is a highly heterogeneous disease. Here, we aimed to investigate the clinical and genetic characteristics of two Chinese pedigrees and summarize the advance in GS genetics, diagnosis and management. Subjects and methods Two three-generation families with GS were identified and screened for mutations in the SLC12A3 gene. Genotype-phenotype correlations were analysed. Results The two probands (A and B) were characterized by hypokalaemia, hypomagnesaemia and hypocalciuria without hypertension. Complete DNA sequencing of the SLC12A3 gene revealed two novel compound heterozygous mutations (c.179C>T and c.234delG; c.486-490delTACGGinsA and c.1925G>A), which are predicted to drastically affect normal protein structure. The female members of the pedigrees showed mild-to-no phenotype, although they carried the same mutations as the probands. Moreover, proband B presented with more severe symptoms than did proband A, which might be related to a lower serum magnesium level. During the 1-year follow-up, both probands showed satisfactory symptom improvement following the use of potassium and magnesium supplements. Conclusion Our findings strongly suggested that the two novel mutations in the SLC12A3 gene are the causative agents of GS, which may provide further insights into the function of this gene and help clinicians better understand this disorder.