title: A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review.
abstract: OBJECTIVE
  Gitelman syndrome (GS) is an autosomal recessive disease characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and hypocalciuria which is caused by mutations in the SLC12A3 gene. In this study, we reported a case of GS pedigree and reviewed pertinent literature so as to explore the relationship between clinical characteristics and genotype meanwhile provide recommendations for the diagnosis and treatment of GS.
  
  
  METHODS
  This is a pedigree-based genetic study of GS and 11 members from one family were included. We summarized their clinical features, analyzed laboratory parameters related to GS and SLC12A3 gene.
  
  
  RESULTS
  The proband experienced intermittent severe symptoms of weakness accompanied by significant hypokalemia, hypomagnesemia and hypocalciuria in laboratory test with poor treatments. His mother had more slight symptoms of weakness than him with mild hypokalemia and hypocalciuria. Mild hypomagnesemia was also observed in his sister with occasional weakness. All other pedigree members had normal laboratory test with no GS-related symptoms. A homozygous mutation of SLC12A3 gene (c.488C > T) was detected by genetic testing in three members, and six were carriers of this mutation.
  
  
  CONCLUSIONS
  Genotype and phenotype vary significantly among GS patients. Male patients tend to experience more severe symptoms and poor treatment effect. Further large-scale population, animal, and molecular biology experiments are required to investigate the complexity of GS and to find a better treatment regimen for this disease.
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Lü
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: West China School of Medicine, Sichuan University, No.17, the 3rd section of the south of Renmin road, Chengdu, 610041, China.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China.
authors.forename: Z
authors.initials: Z
authors.lastname: An
authors.affiliation: West China School of Medicine, Sichuan University, No.17, the 3rd section of the south of Renmin road, Chengdu, 610041, China.
authors.forename: S
authors.initials: S
authors.lastname: Wei
authors.affiliation: West China School of Medicine, Sichuan University, No.17, the 3rd section of the south of Renmin road, Chengdu, 610041, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China.
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, China. buddyjun@hotmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Tong
mesh_terms: D000328:Adult; D044466:Asian People; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D053579:Gitelman Syndrome / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics
chemical_list: C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3
keywords: Gitelman Syndrome; Homozygous mutation; Pedigree; SLC12A3 gene