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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1998-4-7
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pubmed:abstractText |
Distal renal tubular acidosis (dRTA) is characterized by defective urinary acidification by the distal nephron. Cl-/HCO3- exchange mediated by the AE1 anion exchanger in the basolateral membrane of type A intercalated cells is thought to be an essential component of lumenal H+ secretion by collecting duct intercalated cells. We evaluated the AE1 gene as a possible candidate gene for familial dRTA. We found in three unrelated families with autosomal dominant dRTA that all clinically affected individuals were heterozygous for a single missense mutation encoding the mutant AE1 polypeptide R589H. Patient red cells showed approximately 20% reduction in sulfate influx of normal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid sensitivity and pH dependence. Recombinant kidney AE1 R589H expressed in Xenopus oocytes showed 20-50% reduction in Cl-/Cl- and Cl-/HCO3- exchange, but did not display a dominant negative phenotype for anion transport when coexpressed with wild-type AE1. One apparently unaffected individual for whom acid-loading data were unavailable also was heterozygous for the mutation. Thus, in contrast to previously described heterozygous loss-of-function mutations in AE1 associated with red cell abnormalities and apparently normal renal acidification, the heterozygous hypomorphic AE1 mutation R589H is associated with dominant dRTA and normal red cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AlperS LSL,
pubmed-author:BrouilletteJJ,
pubmed-author:BrugnaraCC,
pubmed-author:Guay-WoodfordL MLM,
pubmed-author:HerrinJ TJT,
pubmed-author:JarolimPP,
pubmed-author:JiangLL,
pubmed-author:PrabakaranDD,
pubmed-author:RubinH LHL,
pubmed-author:SeemanovaEE,
pubmed-author:ShayakulCC,
pubmed-author:SimovaSS,
pubmed-author:SomersM JMJ,
pubmed-author:Stuart-TilleyAA,
pubmed-author:ZavadilJJ
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6380-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9497368-Acidosis, Renal Tubular,
pubmed-meshheading:9497368-Anion Exchange Protein 1, Erythrocyte,
pubmed-meshheading:9497368-Antiporters,
pubmed-meshheading:9497368-Bicarbonates,
pubmed-meshheading:9497368-Chloride-Bicarbonate Antiporters,
pubmed-meshheading:9497368-Chlorides,
pubmed-meshheading:9497368-Chromosomes, Human, Pair 17,
pubmed-meshheading:9497368-Erythrocytes,
pubmed-meshheading:9497368-Female,
pubmed-meshheading:9497368-Genes, Dominant,
pubmed-meshheading:9497368-Genetic Linkage,
pubmed-meshheading:9497368-Genetic Markers,
pubmed-meshheading:9497368-Haplotypes,
pubmed-meshheading:9497368-Heterozygote,
pubmed-meshheading:9497368-Humans,
pubmed-meshheading:9497368-Male,
pubmed-meshheading:9497368-Microsatellite Repeats,
pubmed-meshheading:9497368-Mutation,
pubmed-meshheading:9497368-Phenotype,
pubmed-meshheading:9497368-Recombinant Proteins,
pubmed-meshheading:9497368-Sulfates
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pubmed:year |
1998
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pubmed:articleTitle |
Autosomal dominant distal renal tubular acidosis is associated in three families with heterozygosity for the R589H mutation in the AE1 (band 3) Cl-/HCO3- exchanger.
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pubmed:affiliation |
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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