Identification of novel mutations in Na-Cl cotransporter gene in a Korean patient with atypical Gitelman's syndrome

Abstract

The authors report the case of a 20-year-old man with unexplained hypokalemia and metabolic alkalosis suggesting hypokalemic tubulopathy. Interestingly, he showed a mixed phenotype of Gitelman's syndrome (GS) and Bartter's syndrome, which includes normomagnesemia, normal renal magnesium excretion, and hypocalciuria. Renal clearance study showed the presence of a critical defect in the distal nephron rather than loop of Henle. Further family study showed that his mother had a definitive phenotype of GS. By the molecular genetic analysis of these patients, 7 different mutations of the NCCT gene were identified consisting of 3 missense, 1 splice site, and 3 silent mutations. Four of these mutations were novel. The authors emphasize that the combination of a molecular genetic approach and renal clearance study could be of practical benefit in confusing clinical setting and support new diagnostic criteria in GS.