Bartter Syndrome-Related Variants Distribution: Brazilian Data and Its Comparison with Worldwide Cohorts

Nephron. 2023;147(8):478-495. doi: 10.1159/000528557. Epub 2023 Mar 7.

Abstract

Background: Genetic testing is recommended for accurate diagnosis of Bartter syndrome (BS) and serves as a basis for implementing specific target therapies. However, populations other than Europeans and North Americans are underrepresented in most databases and there are uncertainties in the genotype-phenotype correlation. We studied Brazilian BS patients, an admixed population with diverse ancestry.

Methods: We evaluated the clinical and mutational profile of this cohort and performed a systematic review of BS mutations from worldwide cohorts.

Results: Twenty-two patients were included; Gitelman syndrome was diagnosed in 2 siblings with antenatal BS and congenital chloride diarrhea in 1 girl. BS was confirmed in 19 patients: BS type 1 in 1 boy (antenatal BS); BS type 4a in 1 girl and BS type 4b in 1 girl, both of them with antenatal BS and neurosensorial deafness; BS type 3 (CLCNKB mutations): 16 cases. The deletion of the entire CLCNKB (1-20 del) was the most frequent variant. Patients carrying the 1-20 del presented earlier manifestations than those with other CLCNKB-mutations and the presence of homozygous 1-20 del was correlated with progressive chronic kidney disease. The prevalence of the 1-20 del in this BS Brazilian cohort was similar to that of Chinese cohorts and individuals of African and Middle Eastern descent from other cohorts.

Conclusion: This study expands the genetic spectrum of BS patients with different ethnics, reveals some genotype/phenotype correlations, compares the findings with other cohorts, and provides a systematic review of the literature on the distribution of BS-related variants worldwide.

Keywords: Bartter syndrome; Brazilian cohort; CLCNKB mutation; Gitelman syndrome; Pseudo-Bartter syndrome.

Publication types

  • Systematic Review

MeSH terms

  • Bartter Syndrome* / genetics
  • Brazil
  • Chloride Channels / genetics
  • Female
  • Humans
  • Mutation
  • Phenotype
  • Pregnancy
  • Solute Carrier Family 12, Member 1 / genetics

Substances

  • Solute Carrier Family 12, Member 1
  • CLCNKB protein, human
  • Chloride Channels