Novel Compound Heterozygous Mutation in the KCNJ1 Gene Causes Bartter Syndrome

Bartter syndrome type II is an autosomal recessive salt-losing tubulopathy caused by variants in the KCNJ1 gene, with a typical clinical phenotype of hypokalemia. In this study, we identified a 3-year-old child exhibiting hypokalemia and lower limb weakness. Genetic analysis identified a novel compound heterozygous mutation in the KCNJ1 gene (c.640A>G, p.Thr214Ala; c.1017C>A, p.Cys339Ter) in the patient, whereas each of the unaffected parents carried only one of these heterozygous mutations. Structural analysis indicated that the p.Thr214Ala variant impairs the stability of ROMK protein. Our findings expand the phenotypic and genetic spectrum associated with the KCNJ1 gene, which would facilitate genetic counselling and prenatal genetic diagnosis.