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As the most frequent inherited tubulopathy, Gitelman syndrome (GS), has an incidence that has increased worldwide. The distribution of SLC12A3 gene mutation hotspots deserves exploration. In addition, GS is not a benign syndrome; however, the diagnostic process of GS has not yet been completely detailed. We report two cases of GS pedigrees involving two previously unreported mutations, c. 676GA, p. A226T and c. 421GA, p. G141R, in the gene and reviewed relevant literature. We searched the literature for nucleotide of in