A heterozygous missense mutation in the AEI CT/HCO3 exchanger gene cosegregates with autosomal dominant distal renal tubular acidosis (dRTA) in two unrelated families.
ASN 30th Annual Meeting, San Antonio
J Am Soc Nephrol (Sep) 8:386A 1997
Synopsis: Two families with autosomal dominant dRTA were screened for mutations in the gene for the AE1 Cl/HCO3 anion exchanger (the transporter for bicarbonate exit from collecting duct intercalated cells). A point mutation in exon 14 (Arg 589->His) was found in both families. In contrast, patients with hereditary spherocytosis (HS), another syndrome caused by mutations in AE1, had no apparent acidification defects. RBC from the dRTA patients showed slightly reduced anion exchange (sulfate influx) compared with normals or HS patients, but other biochemical indices in dRTA patients were normal. The minimal decrease in AE1 transport kinetics seemingly cannot account for the severity of the acidification defect.
Comment: A recent paper (J Clin Invest 100:1693-707, 1996) described two other mutations in AE1 causing autosomal dominant dRTA: Arg 589->Cys mutations in two families, and Ser 613->Phe in one family. Slight abnormalities in anion transport were found in the RBC from the dRTA patients that were not enough to account for the clinical phenotype. The present study extends this analysis by emphasizing the essential role of Arg 589 in normal urinary acidification. Both of these studies reached the same intriguing conclusion that the defect is not due to a transport abnormality. Perhaps this portion of the AE1 protein interacts with cellular proteins essential for the regulation of bicarbonate transport in the intercalated cell. (Stephen L. Gluck MD, Washington University School of Medicine, St. Louis, MO)
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ASN 30th Annual Meeting, San Antonio
Acidosis/alkalosis : Metabolic acidosis