Simultaneous mutations in the CLCNKB and SLC12A3 genes in two siblings with phenotypic heterogeneity in classic Bartter syndrome

Alberto Bettinelli, Nicolò Borsa, Marie Louise Syrén, Camilla Mattiello, Domenico Coviello, Alberto Edefonti, Marisa Giani, Maurizio Travi, Silvana Tedeschi

Research output: Contribution to journalArticlepeer-review

Abstract

Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide-sensitive NaCl co-transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The children were finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.

Original languageEnglish
Pages (from-to)1269-1273
Number of pages5
JournalPediatric Research
Volume58
Issue number6
DOIs
Publication statusPublished - Dec 2005

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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