title: Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene.
abstract: All affected patients in four families with autosomal dominant familial renal tubular acidosis (dRTA) were heterozygous for mutations in their red cell HCO3-/Cl- exchanger, band 3 (AE1, SLC4A1) genes, and these mutations were not found in any of the nine normal family members studied. The mutation Arg589--> His was present in two families, while Arg589--> Cys and Ser613--> Phe changes were found in the other families. Linkage studies confirmed the co-segregation of the disease with a genetic marker close to AE1. The affected individuals with the Arg589 mutations had reduced red cell sulfate transport and altered glycosylation of the red cell band 3 N-glycan chain. The red cells of individuals with the Ser613--> Phe mutation had markedly increased red cell sulfate transport but almost normal red cell iodide transport. The erythroid and kidney isoforms of the mutant band 3 proteins were expressed in Xenopus oocytes and all showed significant chloride transport activity. We conclude that dominantly inherited dRTA is associated with mutations in band 3; but both the disease and its autosomal dominant inheritance are not related simply to the anion transport activity of the mutant proteins.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, United Kingdom.
authors.forename: L J
authors.initials: LJ
authors.lastname: Bruce
authors.forename: D L
authors.initials: DL
authors.lastname: Cope
authors.forename: G K
authors.initials: GK
authors.lastname: Jones
authors.forename: A E
authors.initials: AE
authors.lastname: Schofield
authors.forename: M
authors.initials: M
authors.lastname: Burley
authors.forename: S
authors.initials: S
authors.lastname: Povey
authors.forename: R J
authors.initials: RJ
authors.lastname: Unwin
authors.forename: O
authors.initials: O
authors.lastname: Wrong
authors.forename: M J
authors.initials: MJ
authors.lastname: Tanner
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000378:metabolism; D000141:Acidosis, Renal Tubular / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics* / Q000378:metabolism; D000838:Anions / Q000378:metabolism; D001120:Arginine / Q000235:genetics; D001692:Biological Transport; D002648:Child; D002675:Child, Preschool; D004913:Erythrocytes, Abnormal / Q000502:physiology*; D005260:Female; D008040:Genetic Linkage; D006031:Glycosylation; D006801:Humans; D007454:Iodides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011994:Recombinant Proteins / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D012694:Serine / Q000235:genetics; D013431:Sulfates / Q000378:metabolism
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D007454:Iodides; D011994:Recombinant Proteins; D013431:Sulfates; D012694:Serine; D001120:Arginine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid