Paula Cristina Barros Pereira1, Flávia Medeiros Melo1, Luiz Armando Cunha De Marco2, Eduardo Araújo Oliveira3, Débora Marques Miranda3, Ana Cristina Simões e Silva4. 1. Instituto Nacional de Ciência e Tecnologia - Medicina Molecular (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil. 2. 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. 3. 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. 4. 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.
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.
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: Sílvia Bouissou Morais Soares; Luiz Alberto Wanderley de Menezes Silva; Flávia Cristina de Carvalho Mrad; Ana Cristina Simões E Silva Journal: World J Pediatr Date: 2019-05-11 Impact factor: 2.764
Authors: Laura I Escobar; Christopher Simian; Cyrielle Treard; Donia Hayek; Carolina Salvador; Norma Guerra; Mario Matos; Mara Medeiros; Sandra Enciso; María Dolores Camargo; Rosa Vargas-Poussou Journal: Mol Genet Genomic Med Date: 2016-02-14 Impact factor: 2.183