Cargando…

Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families

BACKGROUND: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial de...

Descripción completa

Detalles Bibliográficos
Autores principales: Escobar, Laura I., Simian, Christopher, Treard, Cyrielle, Hayek, Donia, Salvador, Carolina, Guerra, Norma, Matos, Mario, Medeiros, Mara, Enciso, Sandra, Camargo, María Dolores, Vargas‐Poussou, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867564/
https://www.ncbi.nlm.nih.gov/pubmed/27247958
http://dx.doi.org/10.1002/mgg3.205
_version_ 1782432042810605568
author Escobar, Laura I.
Simian, Christopher
Treard, Cyrielle
Hayek, Donia
Salvador, Carolina
Guerra, Norma
Matos, Mario
Medeiros, Mara
Enciso, Sandra
Camargo, María Dolores
Vargas‐Poussou, Rosa
author_facet Escobar, Laura I.
Simian, Christopher
Treard, Cyrielle
Hayek, Donia
Salvador, Carolina
Guerra, Norma
Matos, Mario
Medeiros, Mara
Enciso, Sandra
Camargo, María Dolores
Vargas‐Poussou, Rosa
author_sort Escobar, Laura I.
collection PubMed
description BACKGROUND: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial deafness is associated. dRTA is developed during the first months of life and the main manifestations are failure to thrive, vomiting, dehydration, and anorexia. METHODS: Nine unrelated families were studied: seven children, a teenager, and an adult with dRTA. Hearing was preserved in four children. Coding regions of the genes responsible for recessive dRTA were analysed by Sanger sequencing. RESULTS: Molecular defects were found in the genes ATP6V1B1 and ATP6V0A4. We identified three homozygous variants in ATP6V1B: a frameshift mutation (p.Ile386Hisfs*56), a nucleotide substitution in exon 10 (p.Pro346Arg), and a new splicing mutation in intron 5. Three patients were homozygous for one novel (p.Arg743Trp) and one known (p.Asp411Tyr) missense mutations in the ATP6V0A4 gene. Three patients were compound heterozygous: one proband displayed two novel mutations, the frameshift mutation p.Val52Metfs*25, and a large deletion of exons 18–21; two probands showed the missense mutation p.Asp411Tyr and as a second mutation, p.Arg194Ter and c.1691+2dup, respectively. CONCLUSION: ATP6V0A4 and ATP6V1B1 genes were involved in recessive dRTA of Mexican families. All ATP6V1B1 mutations detected were homozygous and all patients developed sensorineural hearing loss (SNHL) early in infancy. ATP6V0A4 mutations were found in one infant and three children without SNHL, and in one teenager and one adult with SNHL confirming the phenotypic variability in this trait. The mutation p.Asp411Tyr detected in four Mexican families was due to a founder effect. Screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA in this population.
format Online
Article
Text
id pubmed-4867564
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-48675642016-05-31 Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families Escobar, Laura I. Simian, Christopher Treard, Cyrielle Hayek, Donia Salvador, Carolina Guerra, Norma Matos, Mario Medeiros, Mara Enciso, Sandra Camargo, María Dolores Vargas‐Poussou, Rosa Mol Genet Genomic Med Original Articles BACKGROUND: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial deafness is associated. dRTA is developed during the first months of life and the main manifestations are failure to thrive, vomiting, dehydration, and anorexia. METHODS: Nine unrelated families were studied: seven children, a teenager, and an adult with dRTA. Hearing was preserved in four children. Coding regions of the genes responsible for recessive dRTA were analysed by Sanger sequencing. RESULTS: Molecular defects were found in the genes ATP6V1B1 and ATP6V0A4. We identified three homozygous variants in ATP6V1B: a frameshift mutation (p.Ile386Hisfs*56), a nucleotide substitution in exon 10 (p.Pro346Arg), and a new splicing mutation in intron 5. Three patients were homozygous for one novel (p.Arg743Trp) and one known (p.Asp411Tyr) missense mutations in the ATP6V0A4 gene. Three patients were compound heterozygous: one proband displayed two novel mutations, the frameshift mutation p.Val52Metfs*25, and a large deletion of exons 18–21; two probands showed the missense mutation p.Asp411Tyr and as a second mutation, p.Arg194Ter and c.1691+2dup, respectively. CONCLUSION: ATP6V0A4 and ATP6V1B1 genes were involved in recessive dRTA of Mexican families. All ATP6V1B1 mutations detected were homozygous and all patients developed sensorineural hearing loss (SNHL) early in infancy. ATP6V0A4 mutations were found in one infant and three children without SNHL, and in one teenager and one adult with SNHL confirming the phenotypic variability in this trait. The mutation p.Asp411Tyr detected in four Mexican families was due to a founder effect. Screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA in this population. John Wiley and Sons Inc. 2016-02-14 /pmc/articles/PMC4867564/ /pubmed/27247958 http://dx.doi.org/10.1002/mgg3.205 Text en © 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Escobar, Laura I.
Simian, Christopher
Treard, Cyrielle
Hayek, Donia
Salvador, Carolina
Guerra, Norma
Matos, Mario
Medeiros, Mara
Enciso, Sandra
Camargo, María Dolores
Vargas‐Poussou, Rosa
Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title_full Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title_fullStr Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title_full_unstemmed Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title_short Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families
title_sort mutations in atp6v1b1 and atp6v0a4 genes cause recessive distal renal tubular acidosis in mexican families
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867564/
https://www.ncbi.nlm.nih.gov/pubmed/27247958
http://dx.doi.org/10.1002/mgg3.205
work_keys_str_mv AT escobarlaurai mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT simianchristopher mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT treardcyrielle mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT hayekdonia mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT salvadorcarolina mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT guerranorma mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT matosmario mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT medeirosmara mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT encisosandra mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT camargomariadolores mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies
AT vargaspoussourosa mutationsinatp6v1b1andatp6v0a4genescauserecessivedistalrenaltubularacidosisinmexicanfamilies