Autosomal dominant distal renal tubular acidosis caused by a mutation in the anion exchanger 1 gene in a Japanese family

Abstract

Autosomal dominant distal renal tubular acidosis (dRTA) is a rare disorder caused by a mutation in the AE1 gene encoding the chloride-bicarbonate (Cl^-/HCO₃^-) anion exchanger 1 (AE1). Most patients with this disorder present with clinical symptoms in adulthood and their phenotype is milder than that of those with autosomal recessive dRTA. In this report, we describe a Japanese family with autosomal dominant dRTA in which the mother and her daughter presented with severe symptoms caused by hypokalemia at 2 years of age. The heterozygous AE1 mutation G609R, which is a known causative mutation of dRTA, was identified in both patients. To our knowledge, this is the first report of a Japanese family with autosomal dominant type dRTA caused by an AE1 mutation. We, therefore, propose that alterations of AE1 should be considered causative of autosomal dominant dRTA even if typical symptoms appear during early childhood and the clinical features are severe.

Keywords: Anion exchanger 1; Autosomal dominant; Distal renal tubular acidosis; Dominant negative; Hypokalemia; SLC4A1.

Fig. 1

AE1 mutation analysis of the patient (a, sense) and her mother (b, antisense). Both individuals were shown to carry the heterozygous missense mutation G609R (Gly609Arg) in AE1 exon 15