Tags

Type your tag names separated by a space and hit enter

Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families.
Mol Genet Genomic Med 2016; 4(3):303-11MG

Abstract

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.

Authors+Show Affiliations

Departamento de Fisiología Facultad de Medicina Universidad Nacional Autónoma de México Mexico City Mexico.Département de Génetique Hôpital Européen Georges Pompidou Paris France.Département de Génetique Hôpital Européen Georges Pompidou Paris France.Département de Génetique Hôpital Européen Georges Pompidou Paris France.Departamento de Fisiología Facultad de Medicina Universidad Nacional Autónoma de México Mexico City Mexico.Servicio de Nefrología Hospital General del Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS) Mexico City Mexico.Servicio de Nefrología Hospital General del Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS) Mexico City Mexico.Laboratorio de Investigación en Nefrología Hospital Infantil de México Federico Gómez Mexico City Mexico.Laboratorio de Investigación en Nefrología Hospital Infantil de México Federico Gómez Mexico City Mexico.UMAE Hospital de Especialidades Centro Médico Nacional del Noreste, IMSS No. 25. Monterrey Mexico.Département de Génetique Hôpital Européen Georges Pompidou Paris France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27247958

Citation

Escobar, Laura I., et al. "Mutations in ATP6V1B1 and ATP6V0A4 Genes Cause Recessive Distal Renal Tubular Acidosis in Mexican Families." Molecular Genetics & Genomic Medicine, vol. 4, no. 3, 2016, pp. 303-11.
Escobar LI, Simian C, Treard C, et al. Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. Mol Genet Genomic Med. 2016;4(3):303-11.
Escobar, L. I., Simian, C., Treard, C., Hayek, D., Salvador, C., Guerra, N., ... Vargas-Poussou, R. (2016). Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. Molecular Genetics & Genomic Medicine, 4(3), pp. 303-11. doi:10.1002/mgg3.205.
Escobar LI, et al. Mutations in ATP6V1B1 and ATP6V0A4 Genes Cause Recessive Distal Renal Tubular Acidosis in Mexican Families. Mol Genet Genomic Med. 2016;4(3):303-11. PubMed PMID: 27247958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. AU - Escobar,Laura I, AU - Simian,Christopher, AU - Treard,Cyrielle, AU - Hayek,Donia, AU - Salvador,Carolina, AU - Guerra,Norma, AU - Matos,Mario, AU - Medeiros,Mara, AU - Enciso,Sandra, AU - Camargo,María Dolores, AU - Vargas-Poussou,Rosa, Y1 - 2016/02/14/ PY - 2015/11/03/received PY - 2015/12/15/revised PY - 2015/12/18/accepted PY - 2016/6/2/entrez PY - 2016/6/2/pubmed PY - 2016/6/2/medline KW - Hearing loss KW - hypokalemia KW - nephrocalcinosis KW - renal tubular acidosis SP - 303 EP - 11 JF - Molecular genetics & genomic medicine JO - Mol Genet Genomic Med VL - 4 IS - 3 N2 - 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. SN - 2324-9269 UR - https://www.unboundmedicine.com/medline/citation/27247958/Mutations_in_ATP6V1B1_and_ATP6V0A4_genes_cause_recessive_distal_renal_tubular_acidosis_in_Mexican_families_ L2 - https://doi.org/10.1002/mgg3.205 DB - PRIME DP - Unbound Medicine ER -