title: Founder mutations in the ATP6V1B1 gene explain most Cypriot cases of distal renal tubular acidosis: first prenatal diagnosis.
abstract: OBJECTIVE
  To investigate clinically and genetically all the distal renal tubular acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to perform the first dRTA prenatal diagnosis. We also tried to find any association with sensorineural hearing loss (SNHL) onset and particular mutations.
  
  
  METHODS
  Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed by standard criteria. Prenatal diagnosis was performed for one Cypriot family.
  
  
  RESULTS
  Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be older than 400 years. No genotype- phenotype correlation was found with SNHL. A known (L81P) and a novel mutation (912delT) were found in the Greek family. Prenatal diagnosis was performed for one Cypriot family, after parents' demand, showing that the embryo was a heterozygous carrier.
  
  
  CONCLUSIONS
  Existence of only two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The age of onset of SNHL varies in our patients and probably is not related to ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not satisfactory for some parents who choose prenatal diagnosis to ensure their child's health.
authors.affiliation: Department of Pediatric Nephrology, Archbishop Makarios III Hospital, Nicosia, Cyprus.
authors.forename: Avraam
authors.initials: A
authors.lastname: Elia
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voskarides
authors.forename: Panayiota
authors.initials: P
authors.lastname: Demosthenous
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Michalopoulou
authors.forename: Maria-Adamantia
authors.initials: MA
authors.lastname: Malliarou
authors.forename: Eleni
authors.initials: E
authors.lastname: Georgaki
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Athanasiou
authors.forename: Charalambos
authors.initials: C
authors.lastname: Patsias
authors.forename: Alkis
authors.initials: A
authors.lastname: Pierides
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
mesh_terms: D000141:Acidosis, Renal Tubular / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003535:Cyprus / Q000453:epidemiology; D005260:Female; D018703:Founder Effect; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*; D055815:Young Adult
chemical_list: C509766:ATP6V1B1 protein, human; D025262:Vacuolar Proton-Translocating ATPases