Molecular Investigation of Distal Renal Tubular Acidosis in Tunisia, Evidence for Founder Mutations

Majdi Nagara 1, * Konstantinos Voskarides Sonia Nouira 1 Nizar Ben Halim 1 Rym Kefi 1 Hajer Aloulou 2 Lilia Romdhane 1 Rim Ben Abdallah 2 Faten Ben Rhouma 1 Khaoula Aissa 2 Lamia Boughamoura 2 Thouraya Kammoun 2 Hatem Azzouz 3 Saoussen Abroug 4, 5 Hathemi Ben Turkia 3 Abdelkarim Ayadi 6 Ridha Mrad 7 Imen Chabchoub 2 Mongia Hachicha 2 Jalel Chemli 5 Constantinos Deltas Sonia Abdelhak 1
* Corresponding author
1 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
2 Department of Pediatrics
3 Département de Pédiatrie, Unité des maladies métaboliques héréditaires
4 Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia
5 Pediatric Department
6 Pediatric Department
7 Troubles congénitaux et héréditaires
Abstract : Background: Distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H+ ions in the intercalated cells of the collecting duct. Both autosomal dominant and recessive forms have been described; the latter is also associated with sensorineural hearing loss. Methods: Twenty-two Tunisian families were analyzed for mutations in the ATP6V1B1 and ATP6V0A4 genes by direct sequencing. Dating of the founder mutations was performed. Results: Two founder mutations in the ATP6V1B1 gene were found in 16/27 dRTA cases. The p.Ile386Hisfs*56 founder mutation was estimated to be older than 2400 years and no correlations were found with deafness. For the remaining patients, two mutations in the ATP6V0A4 gene, one of them being novel, were found in three Tunisian cases. The presence of a heterozygous missense mutation p.T30I, of the ATP6V1B1 gene, was identified in six patients, while no mutations of the second gene were detected. No deleterious mutations of either ATP6V1B1 or ATP6V0A were found for the two probands. Conclusion: Our study gives evidence of phenotypic and genotypic heterogeneity of dRTA in the Tunisian population. Five different mutations were found, two of them were due to a founder effect, and screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA.
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Contributor : Institut Pasteur Tunis <>
Submitted on : Thursday, May 25, 2017 - 1:21:01 PM
Last modification on : Friday, July 26, 2019 - 1:19:12 AM

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Majdi Nagara, Konstantinos Voskarides, Sonia Nouira, Nizar Ben Halim, Rym Kefi, et al.. Molecular Investigation of Distal Renal Tubular Acidosis in Tunisia, Evidence for Founder Mutations. Genetic Testing and Molecular Biomarkers, Mary Ann Liebert, Inc., 2014, 18 (11), pp.741 - 748. ⟨10.1089/gtmb.2014.0175⟩. ⟨pasteur-01375052⟩

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