title: Novel NCCT gene mutations as a cause of Gitelman's syndrome and a systematic review of mutant and polymorphic NCCT alleles.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry, Medizinische Poliklinik, Division of Nephrology, University of Bonn, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Reissinger
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Boris
authors.initials: B
authors.lastname: Utsch
authors.forename: Astrid
authors.initials: A
authors.lastname: Prömse
authors.forename: Johannes
authors.initials: J
authors.lastname: Baulmann
authors.forename: Burkhard
authors.initials: B
authors.lastname: Weisser
authors.forename: Hans
authors.initials: H
authors.lastname: Vetter
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: Dirk
authors.initials: D
authors.lastname: Bokemeyer
mesh_terms: D000328:Adult; D000471:Alkalosis / Q000235:genetics*; D000595:Amino Acid Sequence; D002118:Calcium / Q000652:urine; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007008:Hypokalemia / Q000235:genetics*; D008274:Magnesium / Q000097:blood; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D008274:Magnesium; D002118:Calcium