Background: Bartter syndrome (BS) is a rare autosomal recessive genetic disorder, typically characterized by hypokalemic metabolic alkalosis, and sometimes accompanied by hyponatremia and hypochloremia. BS is caused by mutations at multiple gene loci with strong genetic heterogeneity, making accurate genetic analysis crucial for diagnosis. Case: We collected peripheral blood samples from three family members: an 8-week pregnant woman, her husband, and their daughter, with BS symptoms. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed, with variants verified by Sanger sequencing. Minigene assays were used to investigate splicing effects, and in silico predictions were conducted to assess the impact of mutations on protein structure. A prenatal diagnosis was performed at 18 weeks of gestation via amniocentesis and Sanger sequencing. Conclusions: This case highlights three critical values. First, clinically, WGS provides a feasible solution for diagnosing BS cases with negative WES results, which helps reduce hypokalemia-related complications. Second, this is the first report of the SLC12A1 c.2961-647T>G and c.1153G>A variants, and integrated validation confirms their pathogenicity, expanding the spectrum of pathogenic SLC12A1 variants. Third, our findings guide clinicians to consider deep intronic variants and WGS application in unexplained hereditary renal diseases, which is highly relevant to current prenatal diagnosis and genetic counseling practices. WGS can identify deep intronic variants in SLC12A1, and functional experiments can strengthen pathogenicity evidence, providing an effective prenatal diagnostic approach for families with a history of BS.
Wu et al. (Mon,) studied this question.