A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect.

Abstract

Bartter's syndrome involves an overlapping set of closely related renal tubular disorders that can be subdivided into at least three clinical phenotypes: (1) the hypercalciuric antenatal Bartter variant; (2) the classic Bartter variant; and (3) the hypocalciuric-hypomagnesemic Gitelman variant. Recent data demonstrate that in several phenotypically indistinguishable cohorts, antenatal Bartter's syndrome is genetically heterogeneous. In these patients, mutations in the genes encoding either the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the ATP-regulated potassium channel ROMK (KCNJI) have been identified. A cohort of 20 Costa Rican patients with a congenital syndrome that bears strong similarities to antenatal Bartter's syndrome but also has several distinct features has recently been described. In this cohort, we have identified a predominant mutation that introduces a premature stop in codon W625 of the NKCC2 gene (SCL12A1). This mutant allele is contained on a single common haplotype, suggesting that the majority of antenatal Bartter's syndrome patients in Costa Rica share a single common ancestor.