The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis

Viviana Palazzo, Aldesia Provenzano, Francesca Becherucci, Giulia Sansavini, Benedetta Mazzinghi, Valerio Orlandini, Laura Giunti, Rosa Maria Roperto, Marilena Pantaleo, Rosangela Artuso, Elena Andreucci, Sara Bargiacchi, Giovanna Traficante, Stefano Stagi, Luisa Murer, Elisa Benetti, Francesco Emma, Mario Giordano, Francesca Rivieri, Giacomo ColussiSilvana Penco, Emanuela Manfredini, Maria Rosa Caruso, Livia Garavelli, Simeone Andrulli, Gianluca Vergine, Nunzia Miglietti, Elena Mancini, Cristina Malaventura, Antonio Percesepe, Enrico Grosso, Marco Materassi, Paola Romagnani, Sabrina Giglio

Research output: Contribution to journalArticlepeer-review


Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient.

Original languageEnglish
Pages (from-to)1243-1255
Number of pages13
JournalKidney International
Issue number5
Publication statusPublished - May 1 2017


  • chronic kidney disease
  • deafness
  • distal renal tubular acidosis
  • mutations
  • nephrocalcinosis

ASJC Scopus subject areas

  • Nephrology


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