title: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham 35294, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Kurtz
authors.forename: L
authors.initials: L
authors.lastname: Karolyi
authors.forename: H W
authors.initials: HW
authors.lastname: Seyberth
authors.forename: M C
authors.initials: MC
authors.lastname: Koch
authors.forename: R
authors.initials: R
authors.lastname: Vargas
authors.forename: D
authors.initials: D
authors.lastname: Feldmann
authors.forename: M
authors.initials: M
authors.lastname: Vollmer
authors.forename: N V
authors.initials: NV
authors.lastname: Knoers
authors.forename: G
authors.initials: G
authors.lastname: Madrigal
authors.forename: L M
authors.initials: LM
authors.lastname: Guay-Woodford
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003364:Costa Rica; D004247:DNA / Q000032:analysis; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D028021:Sodium-Potassium-Chloride Symporters; D004247:DNA