title: Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis.
abstract: Primary distal renal tubular acidosis (dRTA) type I is a hereditary renal tubular disorder, which is characterized by impaired renal acid secretion resulting in metabolic acidosis. Clinical symptoms are nephrocalcinosis, nephrolithiasis, osteomalacia, and growth retardation. Biochemical alterations consist of hyperchloremic metabolic acidosis, hypokalemia with muscle weakness, hypercalciuria, and inappropriately raised urinary pH. Autosomal dominant and rare forms of recessive dRTA are known to be caused by mutations in the gene for the anion exchanger AE1. In order to identify a gene responsible for recessive dRTA, we performed a total genome scan with 303 polymorphic microsatellite markers in six consanguineous families with recessive dRTA from Turkey. In four of these there was an association with sensorineural deafness. The total genome scan yielded regions of homozygosity by descent in all six families on chromosomes 1, 2, and 10 as positional candidate region. In one of these regions the gene ATP6B1for the ss1 subunit of the vacuolar H(+)-ATPase is localized, which has recently been identified as causative for recessive dRTA with sensorineural deafness. Therefore, we conducted mutational analysis in 15 families and identified potential loss-of-function mutations in ATP6B1in 8. We thus confirmed that defects in this gene are responsible for recessive dRTA with sensorineural deafness.
authors.affiliation: University Children's Hospital, Mathildenstrasse 1, 79106 Freiburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ruf
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rensing
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.forename: Lisa
authors.initials: L
authors.lastname: Guay-Woodford
authors.forename: Cornelia
authors.initials: C
authors.lastname: Klein
authors.forename: Martin
authors.initials: M
authors.lastname: Vollmer
authors.forename: Edgar
authors.initials: E
authors.lastname: Otto
authors.forename: Frank
authors.initials: F
authors.lastname: Beekmann
authors.forename: Maria
authors.initials: M
authors.lastname: Haller
authors.forename: Alexander
authors.initials: A
authors.lastname: Wiedensohler
authors.forename: Ernst
authors.initials: E
authors.lastname: Leumann
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Rizzoni
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandis
authors.forename: James L
authors.initials: JL
authors.lastname: Weber
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics*; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011257:Pregnancy Proteins; D017494:Proton Pumps / Q000235:genetics*; D006180:Proton-Translocating ATPases; D013491:Suppressor Factors, Immunologic; D025262:Vacuolar Proton-Translocating ATPases
chemical_list: D011257:Pregnancy Proteins; D017494:Proton Pumps; D013491:Suppressor Factors, Immunologic; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases