A Novel Mutation in the Anion Exchanger 1 Gene Is Associated With Familial Distal Renal Tubular Acidosis and Nephrocalcinosis

Objective. The anion exchanger gene (AE1) or band 3 encodes a chloride-bicarbonate (Cl−/HCO3−) exchanger expressed in the erythrocyte and in the renal α-intercalated cells involved in urine acidification. The purpose of the present study was to screen for mutations in the AE1 gene in 2 brothers (10 and 15 years of age) with familial distal renal tubular acidosis (dRTA), nephrocalcinosis, and failure to thrive. Methods. AE1 mutations were screened by single-strand conformation polymorphism, cloning, and sequencing. Results. A complete form of dRTA was confirmed in the 2 affected brothers and an incomplete form in their father. All 3 were heterozygous for a novel 20-bp deletion in exon 20 of the AE1 gene. This deletion resulted in 1 mutation in codon 888 (Ala-888→Leu) followed by a premature termination codon at position 889, truncating the protein by 23 amino acids. As band 3 deficiency might lead to spherocytic hemolytic anemia or ovalocytosis, erythrocyte abnormalities were also investigated, but no morphologic changes in erythrocyte membrane were found and the osmotic fragility test was normal. Conclusions. A novel mutation in the AE1 gene was identified in association with autosomal dominant dRTA. We suggest that RTA be considered a diagnostic possibility in all children with failure to thrive and nephrocalcinosis.