title: Genetic Features of Chinese Patients with Gitelman Syndrome: Sixteen Novel SLC12A3 Mutations Identified in a New Cohort.
abstract: Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy caused by inactivating mutations in the SLC12A3 gene. Although hundreds of different mutations across the SLC12A3 gene have been reported worldwide, data from mainland China are limited. We investigated the clinical manifestations and genetic features of Chinese patients with GS.
  
  
  
  Fifty-four unrelated Chinese patients with clinically diagnosed GS were included. Clinical manifestations and biochemical parameters were collected and analyzed. All exons and flanking regions of the SLC12A3 and CLCNKB genes were screened by direct sequencing.
  
  
  
  Weakness was the most commonly reported symptom in this cohort of patients with GS. In gender-based analyses, higher systolic blood pressure and urine protein excretion were observed in male patients. For genetic screening, 2 pathogenic SLC12A3 mutations were identified in 38 patients (70.4%), 1 mutation in 11 patients (20.4%) and no mutation in 5 patients (9.3%). In total, 42 distinct pathogenic mutations throughout SLC12A3 were identified; 16 were novel, including 9 missense, 1 deletion, 1 insertion, 3 splice site and 2 nonsense mutations. Eleven mutations were recurrently found in different patients. Among them, T60M and D486N were identified in 11 individuals. No CLCNKB mutations were found.
  
  
  
  Sixteen novel SLC12A3 pathogenic mutations were identified in a cohort of Chinese patients with GS. T60M and D486N were most frequent and appear to be important candidate alleles in Chinese patients with GS.
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Chunli
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Xie
authors.forename: Ping-Yan
authors.initials: PY
authors.lastname: Shen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Xiao-Nong
authors.initials: XN
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China; D018118:Chloride Channels / Q000235:genetics*; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D053579:Gitelman Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics; D055815:Young Adult
chemical_list: C412733:CLCNKB protein, human; D018118:Chloride Channels; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3