title: Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome.
abstract: BACKGROUND
  Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman's syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene.
  
  
  METHODS
  We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 +/- 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis.
  
  
  RESULTS
  We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346-353delACTGATGG) and 1 in-frame insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883-2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene.
  
  
  CONCLUSIONS
  Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify.
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Shao
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Feng
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000706:statistics & numerical data*; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D053579:Gitelman Syndrome / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters