title: [From gene to disease; mutations in the SLC12A3 gene as the cause of Gitelman's syndrome].
abstract: Gitelman's syndrome is characterised by persistent hypokalaemia, hypomagnesaemia and hypocalciuria (OMIM 263800). This rare autosomal recessive disorder is caused by renal Na+, Cl-, K+ and Mg2+ wasting. Other typical features include hypocalciuria and an intact renal concentrating ability. Gitelman's syndrome is caused by mutations in the SLC12A3 gene, encoding the thiazide-sensitive sodium-chloride co-transporter (NCC). NCC is located in the distal convoluted tubule of the kidney, a segment known to play an important role in active magnesium reabsorption in the nephron. The exact mechanisms underlying hypomagnesaemia and hypocalciuria in Gitelman's syndrome are still poorly understood, but point to enhanced proximal Na+ and Ca2+ reabsorption and apoptosis of distal convoluted tubule cells.
authors: Afd. Kindernefrologie, Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen. m.cornelissen@cukz.umcn.nl
authors: E A M
authors: EA
authors: Cornelissen
authors: R J M
authors: RJ
authors: Bindels
authors: L H
authors: LH
authors: Hoefsloot
authors: N V A M
authors: NV
authors: Knoers
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D007686:Kidney Tubules, Distal / Q000378:metabolism / Q000503:physiopathology; D008274:Magnesium / Q000378:metabolism*; D011955:Receptors, Drug / Q000235:genetics*; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics* / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*; D013577:Syndrome
chemical_list: D002712:Chlorides; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D012964:Sodium; D008274:Magnesium; D002118:Calcium