title: Molecular investigation of distal renal tubular acidosis in Tunisia, evidence for founder mutations.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Biomedical Genomics and Oncogenetics Laboratory LR11IPT05, Institut Pasteur de Tunis, Université Tunis El Manar , Tunis, Tunisia .
authors.forename: Majdi
authors.initials: M
authors.lastname: Nagara
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voskarides
authors.forename: Sonia
authors.initials: S
authors.lastname: Nouira
authors.forename: Nizar
authors.initials: N
authors.lastname: Ben Halim
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.forename: Hajer
authors.initials: H
authors.lastname: Aloulou
authors.forename: Lilia
authors.initials: L
authors.lastname: Romdhane
authors.forename: Rim
authors.initials: R
authors.lastname: Ben Abdallah
authors.forename: Faten
authors.initials: F
authors.lastname: Ben Rhouma
authors.forename: Khaoula
authors.initials: K
authors.lastname: Aissa
authors.forename: Lamia
authors.initials: L
authors.lastname: Boughamoura
authors.forename: Thouraya
authors.initials: T
authors.lastname: Kammoun
authors.forename: Hatem
authors.initials: H
authors.lastname: Azzouz
authors.forename: Saoussen
authors.initials: S
authors.lastname: Abroug
authors.forename: Hathemi
authors.initials: H
authors.lastname: Ben Turkia
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Ayadi
authors.forename: Ridha
authors.initials: R
authors.lastname: Mrad
authors.forename: Imen
authors.initials: I
authors.lastname: Chabchoub
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D018703:Founder Effect; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D014416:Tunisia; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: C509766:ATP6V1B1 protein, human; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases