Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome

Hum Mutat. 2002 Jul;20(1):78. doi: 10.1002/humu.9045.


The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkalosis / blood
  • Alkalosis / genetics*
  • Alkalosis / urine
  • Calcium / urine
  • Carrier Proteins / genetics*
  • DNA / chemistry
  • DNA / genetics
  • Humans
  • Hypokalemia / blood
  • Hypokalemia / genetics*
  • Hypokalemia / urine
  • Italy
  • Magnesium / blood
  • Mutation
  • Mutation, Missense
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Drug*
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Sodium Chloride Symporters
  • Solute Carrier Family 12, Member 3
  • Symporters*
  • Syndrome


  • Carrier Proteins
  • Receptors, Drug
  • SLC12A3 protein, human
  • Sodium Chloride Symporters
  • Solute Carrier Family 12, Member 3
  • Symporters
  • thiazide receptor
  • DNA
  • Magnesium
  • Calcium

Associated data

  • OMIM/263800