title: Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis.
abstract: OBJECTIVE
  Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis due to impaired renal acid excretion. The aim of this study was to demonstrate the genetic diagnosis of four children with dRTA through use of whole-exome sequencing.
  
  
  METHODS
  Two unrelated families were selected; a total of four children with dRTA and their parents, in order to perform whole-exome sequencing. Hearing was preserved in both children from the first family, but not in the second, wherein a twin pair had severe deafness. Whole-exome sequencing was performed in two pooled samples and findings were confirmed with Sanger sequencing method.
  
  
  RESULTS
  Two mutations were identified in the ATP6V0A4 and ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the ATP6V0A4 gene with a single nucleotide change GAC → TAC (c.1232G>T) was found, which caused a substitution of aspartic acid to tyrosine in position 411. In the second family, a homozygous recurrent mutation with one base-pair insertion (c.1149_1155insC) in exon 12 of the ATP6V1B1 gene was detected.
  
  
  CONCLUSIONS
  These results confirm the value of whole-exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Paula Cristina Barros
authors.initials: PC
authors.lastname: Pereira
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Flávia Medeiros
authors.initials: FM
authors.lastname: Melo
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Department of Surgery, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Luiz Armando Cunha
authors.initials: LA
authors.lastname: De Marco
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Department of Pediatrics, Unit of Pediatric Nephrology, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Eduardo Araújo
authors.initials: EA
authors.lastname: Oliveira
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Department of Pediatrics, Unit of Pediatric Nephrology, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Débora Marques
authors.initials: DM
authors.lastname: Miranda
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Department of Pediatrics, Unit of Pediatric Nephrology, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil. Electronic address: acssilva@hotmail.com.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simões e Silva
mesh_terms: D000141:Acidosis, Renal Tubular / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D012720:Severity of Illness Index; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: D025262:Vacuolar Proton-Translocating ATPases
keywords: ATP6V0A4; ATP6V1B1; Acidose tubular renal distal; Children; Crianças; Distal renal tubular acidosis; Genetics; Genética; Sequenciamento total do exoma; Whole-exome sequencing