title: Mutation profile and treatment of Gitelman syndrome in Chinese patients.
abstract: BACKGROUND
  Gitelman syndrome (GS) is a rare autosomal recessive disease caused by loss-of-function mutations in the SLC12A3 gene, and is characterized by hypokalemia and metabolic alkalosis. In this study, we aimed to study the genotype, phenotype, and treatment in 42 GS patients, the largest sample size so far in mainland China.
  
  
  METHODS
  We retrospectively studied the clinical data and genetic characteristics of 42 patients diagnosed with GS in Peking Union Medical College Hospital from 2012 to 2015. Therapeutic efficacy of spironolactone and potassium supplements was also studied retrospectively.
  
  
  RESULTS
  Eighty-one mutation alleles were found in 42 patients, and total of 52 distinctly different mutation alleles were identified, of which 15 were new mutation alleles. p.Asp486Asn was a hotspot in our series, with the allele frequency being 19.7 % (16/81), and was found in 13 patients (31.0 %). Treatment with spironolactone or potassium supplements alone significantly increased serum potassium concentration by 0.36 ± 0.37 and 0.45 ± 0.35 mmol/l, respectively (both P < 0.05), and combined therapy with spironolactone and potassium increased serum potassium concentration by 0.69 ± 0.64 mmol/l (P < 0.05).
  
  
  CONCLUSIONS
  18.5 % (15/81) mutation sites identified in 42 Chinese GS patients are novel. p.Asp486Asn mutation is a hotspot, which is different from the reports from other countries. Spironolactone could moderately elevate serum potassium level, and spironolactone in combination with potassium supplements tended to be more effective.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China. tonganli@hotmail.com.
authors.forename: Anli
authors.initials: A
authors.lastname: Tong
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis; D019587:Dietary Supplements / Q000009:adverse effects; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D020022:Genetic Predisposition to Disease; D053579:Gitelman Syndrome / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011188:Potassium / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012189:Retrospective Studies; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004232:Diuretics; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D013148:Spironolactone; D011188:Potassium
keywords: Genotype; Gitelman syndrome; Pheonotype; Spironolactone; Treatment