Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes
| العنوان: | Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes |
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| المؤلفون: | Saber Hamami, F. Amri, Wafa Ben Romdane, Gustavo Pérez de Nanclares, Donia Elhayek, Amel Haj Khelil, Nadia Leban, Mohamed Neji Gueddiche, Slaheddine Chouchane, Samir M'Rabet, Monia Troudi, Jemni Ben Chibani, Gema Ariceta, Luis Castaño, Adnene Mlika |
| المصدر: | BMC Medical Genetics Addi. Archivo Digital para la Docencia y la Investigación instname |
| بيانات النشر: | BioMed Central, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Vacuolar Proton-Translocating ATPases, ATP6V0A4, Tunisia, Tunisian population, Hearing Loss, Sensorineural, Mutation, Missense, Black People, Biology, medicine.disease_cause, GENETICS AND HEREDITY, Frameshift mutation, Cohort Studies, Exon, Distal renal tubular acidosis, Anion Exchange Protein 1, Erythrocyte, medicine, Genetics, Missense mutation, Humans, Genetics(clinical), Frameshift Mutation, Gene, Genetics (clinical), Mutation, ATP6V1B1, Homozygote, Intron, Infant, Acidosis, Renal Tubular, Exons, medicine.disease, Child, Preschool, Sensorineural hearing loss, Female, Algorithm, Algorithms, Gene Deletion, Research Article |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1471-2350 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d9194b5f2301257c31892f0a0305f02Test http://europepmc.org/articles/PMC4225572Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3d9194b5f2301257c31892f0a0305f02 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712350 |
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