title: Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome.
abstract: OBJECTIVE
  Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic metabolic alkalosis, significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. GS is caused by inactivating variants in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl co-transporter. So far, more than 100 variants have been described in the SLC12A3 gene in Gitelman syndrome.
  
  
  METHODS
  Biochemical parameters in blood and urine were measured and documented. Genomic DNA was extracted from peripheral blood of all patients. Variants were screened for the SLC12A3 and CLCNKB gene by sequencing directly. Reverse-transcription polymerase chain reaction and complementary DNA sequence analysis were performed to confirm deletion or splicing variants.
  
  
  RESULTS
  We identified 13 variants in the SLC12A3 gene in 13 Chinese patients, including 10 missense substitutions, two splicing variants, and one deletion/insertion variant. Five novel variants were identified for the first time in patients with Gitelman syndrome. We did not find any variants in the CLCNKB gene. A homozygous Thr60Met carrier suffered from hypothyroidism and received thyroxine replacement therapy.
  
  
  CONCLUSIONS
  We have identified 13 variants, including five novel variants in the SLC12A3 gene in 13 patients with Gitelman syndrome. T60M is the most frequent variant in our patients. There was no significant correlation between genotype and phenotype in our patients.
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
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: Xiaoxia
authors.initials: X
authors.lastname: Pan
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Pingyan
authors.initials: P
authors.lastname: Shen
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D018118:Chloride Channels / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D053579:Gitelman Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
chemical_list: C412733:CLCNKB protein, human; D018118:Chloride Channels; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters