A COMMON NKCC2 MUTATION IN COSTA-RICAN BARTTERS-SYNDROME PATIENTS - EVIDENCE FOR A FOUNDER EFFECT

Bartter's syndrome involves an overlapping set of closely related rena l tubular disorders that can be subdivided into at least three clinica l phenotypes: (I) the hypercalciuric antenatal Bartter variant; (2) th e classic Bartter variant; and (3) the hypocalciuric-hypomagnesemic Gi telman variant. Recent data demonstrate that in several phenotypically indistinguishable cohorts, antenatal Bartter's syndrome is geneticall y heterogeneous. In these patients, mutations in the genes encoding ei ther the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the AT P-regulated potassium channel ROMK (KCNJ1) have been identified. A coh ort of 20 Costa Rican patients with a congenital syndrome that bears s trong similarities to antenatal Bartter's syndrome but also has severa l distinct features has recently been described. In this cohort, we ha ve identified a predominant mutation that introduces a premature stop in codon W625 of the NKCC2 gene (SCL12A1). This mutant allele is conta ined on a single common haplotype, suggesting that the majority of ant enatal Bartter's syndrome patients in Costa Rica share a single common ancestor.