Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation

J Clin Endocrinol Metab. 2012 Aug;97(8):E1478-82. doi: 10.1210/jc.2012-1707. Epub 2012 Jun 7.


Context and objective: Genotype, phenotype, and follow-up analysis is rarely performed in a large number of patients with Gitelman's syndrome (GS) caused by mutations in SLC12A3 encoding the thiazide-sensitive NaCl cotransporter.

Design, setting, and patients: One hundred seventeen Taiwanese GS patients (70 males and 47 females, age 24 ± 10 yr) with SLC12A3 mutations belonging to 92 unrelated families were investigated. Genomic DNA and/or cDNA from blood leukocytes were analyzed for SLC12A3 mutations and haplotype analysis with intragenic and extragenic markers for recurrent SLC12A3 mutations. Clinical symptoms and biochemical studies at the first presentation as well as follow-up were examined.

Results: Forty different SLC12A3 mutations were identified. Approximately 12% of patients had triple SLC12A3 mutations. Fourteen mutations were recurrent with only one founder effect (S710X). Typical hypocalciuria and hypomagnesemia were not found in seven and nine patients, respectively. In addition to male patients having an earlier age of onset, more severe hypokalemia, and significantly lower serum aldosterone concentration, patients with homozygous and deep mutations in intron 13 (c.1670-191C → T) had more severe phenotype. Seven and five patients had chronic kidney disease (stage III-IV) and type 2 diabetes at the follow-up, respectively.

Conclusion: Screening of recurrent hot spot SLC12A3 mutations may provide an early diagnosis of GS. Besides gender effect, the nature of homozygous and deep intronic mutations may influence the phenotype. Patients with GS may be at increased risk for the development of chronic kidney disease and type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Female
  • Follow-Up Studies
  • Genotype
  • Gitelman Syndrome / complications
  • Gitelman Syndrome / genetics*
  • Humans
  • Male
  • Mutation*
  • Phenotype
  • Receptors, Drug / genetics*
  • Solute Carrier Family 12, Member 3
  • Symporters / genetics*
  • Taiwan


  • Receptors, Drug
  • SLC12A3 protein, human
  • Solute Carrier Family 12, Member 3
  • Symporters