title: Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance.
abstract: We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance.
authors.affiliation: Department of Pediatrics, Division of Nephrology, University of British Columbia, Vancouver, Canada. cmammen@cw.bc.ca
authors.forename: Cherry
authors.initials: C
authors.lastname: Mammen
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Rupps
authors.forename: Peter
authors.initials: P
authors.lastname: Trnka
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D001477:Bartter Syndrome; D002675:Child, Preschool; D004232:Diuretics; D004351:Drug Resistance / Q000235:genetics*; D053579:Gitelman Syndrome / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006967:Hypersensitivity; D008297:Male; D011110:Polymorphism, Genetic; D011955:Receptors, Drug / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*; D049971:Thiazides / Q000494:pharmacology*
chemical_list: D004232:Diuretics; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D049971:Thiazides