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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: Proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes
BMC Medical Genetics, Volume 14, No. 1, Article 119, Year 2013
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Description
Background: Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies.Methods: 25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing.Results: In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c.1102G > A; p.Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p.Met408Cysfs*10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19.Conclusion: Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c.1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL. © 2013 Elhayek et al.; licensee BioMed Central Ltd.
Authors & Co-Authors
Elhayek, Donia
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Spain, Leioa
Universidad Del Pais Vasco
Tunisia, Monastir
Chu Fattouma-bourguiba
Pérez de Nanclares, Gustavo
Spain, Leioa
Universidad Del Pais Vasco
Chouchane, Slaheddine
Tunisia, Monastir
Chu Fattouma-bourguiba
Hamami, Saber
Tunisia, Monastir
Chu Fattouma-bourguiba
Mlika, Adnène
Tunisia, Kairouan
Ibn el Jazar Hospital
Troudi, Monia
Tunisia, Kairouan
Ibn el Jazar Hospital
Leban, Nadia
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Ben Romdane, Wafa
Tunisia, Gabes
Mohamed Ben Sassi Hospital
Gueddiche, Mohamed Néji
Tunisia, Monastir
Chu Fattouma-bourguiba
El Amri, Fethi
Tunisia, Kairouan
Ibn el Jazar Hospital
M’rabet, Samir
Tunisia, Gabes
Mohamed Ben Sassi Hospital
Ben Chibani, Jemni E.
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Castaño, Luis Antonio
Spain, Leioa
Universidad Del Pais Vasco
Haj Khelil, Amel
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Ariceta, Gema
Spain, Leioa
Universidad Del Pais Vasco
Spain, Baracaldo
Osakidetza, Cruces University Hospital
Spain, Barcelona
Hospital Materno-infantil Vall d' Hebron
Statistics
Citations: 39
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.1186/1471-2350-14-119
Research Areas
Cancer
Disability
Genetics And Genomics
Maternal And Child Health
Study Design
Cohort Study
Participants Gender
Male