Novel NCCT gene mutations as a cause of Gitelman's syndrome and a systematic review of mutant and polymorphic NCCT alleles

Kidney Blood Press Res. 2002;25(6):354-62. doi: 10.1159/000068695.


Background: Gitelman's syndrome (GS) is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria and these phenotypic features have been shown to be attributable to mutations in the gene encoding the thiazide-sensitive Na/Cl cotransporter (NCCT). Until now, 55 different mutations have been reported and most of the families affected with GS exhibit autosomal recessive inheritance.

Methods: All 26 exons of the human NCCT gene were investigated in 2 German NCCT-deficient patients and their families. Mutation detection was performed by either direct automated sequencing of polymerase chain reaction (PCR)-amplified DNA products or by sequence analysis of cloned PCR products.

Results: In a 47-year-old German GS female a novel non-conservative missense mutation (S314F) and a complex deletion/insertion in the NCCT gene were found to be associated with the disorder. A further novel non-conservative substitution (S402F) together with a frequently observed R209W exchange were found in a 19-year-old German GS female.

Conclusions: The observation of a compound heterozygote state in both females affected and the absence of a GS phenotype in their relatives carrying a single mutant allele is consistent with an autosomal recessive pattern of inheritance.

Publication types

  • Case Reports
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Alkalosis / genetics*
  • Amino Acid Sequence
  • Calcium / urine
  • Carrier Proteins / genetics*
  • Female
  • Gene Deletion
  • Heterozygote
  • Humans
  • Hypokalemia / genetics*
  • Magnesium / blood
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Receptors, Drug*
  • Sodium Chloride Symporters
  • Solute Carrier Family 12, Member 3
  • Symporters*


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

Associated data

  • OMIM/241200
  • OMIM/263800