Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis
Journal Title: Jornal de Pediatria - Year 2015, Vol 91, Issue 6
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. Conclusion 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 and Affiliations
Ana Cristina Simões-e-Silva
Keywords
Related Articles
- EP ID EP554579
- DOI 10.1016/j.jped.2015.02.002
- Views 53
- Downloads 0
Energy expenditure, growth, and nutritional therapy in appropriate and small for gestational age preterm infants
Objective To evaluate the resting energy expenditure, growth, and quantity of energy and macronutrients intake in a group of preterm newborns. Methods The cohort study was performed with appropriate and small for gestat...
Health-related quality of life in post-infectious bronchiolitis obliterans: agreement between children and their proxy
Objective To assess the level of agreement in health-related quality of life between children with Post-infectious Bronchiolitis Obliterans and their parent (so-called proxy). Methods Participants aged between 8and 17 y...
Health-related physical fitness and weight status in 13- to 15-year-old Latino adolescents. A pooled analysis
Objective The aim of this study was to investigate the relation between health-related physical fitness and weight status in 13- to 15-year-old Latino adolescents. Method The final sample consisted of 73,561 adolescents...
Early changes in adipokines from overweight to obesity in children and adolescents
Objective Childhood obesity has been associated with metabolic syndrome and cardiovascular diseases. This study aimed to compare plasma levels of traditional metabolic markers, adipokines and soluble tumor necrosis facto...
Breastfeeding in Brazil: major progress, but still a long way to go
The innovative and well-designed retrospective study by Oliveira et al. featured in this issue documents encouraging secular trends in breastfeeding duration in Rio de Janeiro during the 1960–2009 period. Study participa...