[Analysis of novel mutations in the SLC12A3 gene of a family with Gitelman syndrome].

This study aimed to identify mutations in the SLC12A3 gene and investigate their role in the pathogenesis of Gitelman syndrome. Sanger sequencing of the SLC12A3 gene was performed using samples from a patient clinically suspected of having Gitelman syndrome, who was admitted to the Department of Endocrinology and Metabolism at Shanghai Fengxian District Central Hospital in August 2024. Upon identification of mutations, the relevant exons were sequenced in her first-degree relatives. Functional predictions of the protein were made using CADD, DANN, MetaSVM, Polyphen2, SIFT, and M-CAP software. A previously unreported missense variant, NM_000339:c.704C>A (p.Thr235Lys), located in exon 16 of SLC12A3, was identified in homozygosity in the proband and in heterozygosity in her daughter. This mutation was absent in all control individuals. Multiple prediction tools consistently indicated that the mutation likely disrupts gene/protein structure or function. The c.704C>A mutation in exon 16 of SLC12A3 is a novel pathogenic variant contributing to the development of Gitelman syndrome.