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Abstract: PO1323

Whole-Exome Sequencing as a First-Line Diagnostic Tool in Bartter and Gitelman Syndromes

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Becherucci, Francesca, Meyer Children's Hospital, Florence, Italy
  • Palazzo, Viviana, Meyer Children's Hospital, Florence, Italy
  • Cirillo, Luigi, Meyer Children's Hospital, Florence, Italy
  • Mazzinghi, Benedetta, Meyer Children's Hospital, Florence, Italy
  • Raglianti, Valentina, Meyer Children's Hospital, Florence, Italy
  • Landini, Samuela, Meyer Children's Hospital, Florence, Italy
  • Romagnani, Paola, Meyer Children's Hospital, Florence, Italy

The clinical diagnosis of Bartter (BS) and Gitelman syndrome (GS) can be challenging, as they are rare and phenotypically overlapping. Thus, genetic testing represents the gold standard for the diagnosis. Next-generation sequencing is increasingly utilized in diagnostics and research of inherited tubulopathies. Sequencing of gene panels achieved high diagnostic yield and new insights into the phenotypic spectrum of these rare disorders. Whole-exome (WES) is not routinely performed for the molecular diagnosis of BS and GS. The aim of our study was to assess the diagnostic performance of WES in BS and GS, to establish genotype-phenotype correlations and to assess cost-effectiveness of this approach.


We performed WES in all consecutive patients referred for genetic testing with a clinical suspect of BS or GS. Variant prioritization was carried out according to ACMG guidelines. Clinical data were collected retrospectively.


We enrolled 50 patients (22 males) with a clinical diagnosis of BS or GS. All the patients showed hypokalemic metabolic alkalosis at onset. The median age at clinical diagnosis was 7 years (range 0-67). WES showed pathogenic variants in 41/50 patients (82%). A dedicated analytic pipeline allowed us to identify copy number variations (CNVs) in 7/41 patients with a confirmed genetic diagnosis. In details, WES allowed us to confirm the clinical diagnosis in 33/50 patients and to change it 8 additional patients (6 patients from BS to GS, 2 patients outside the BS/GS spectum). Nephrocalcinosis was detected in 38% vs 8% of patients with a genetic diagnosis of BS and GS, respecively. Hypomagnesemia was similarly distributed among BS and GS patients (45% vs. 68%). Finally, patients with GS showed a median age at onset higher than patients with BS, but some overlap did exist, making differential diagnosis challenging at single-patient level.


The results of our study demonstrate that WES ensures a high diagnostic yield in patients with a clinical diagnosis of BS or GS, especially if coupled with analysis of CNVs. This approach showed to be useful in dealing with the phenotypic heterogeneity typical of these rare disorders, improving differential diagnosis by detecting phenocopies also outside the BS/GS spectrum.