ClinVar

Toye et al. (2002) reported studies of band-3 Walton, a C-terminal deletion associated with distal renal tubular acidosis (DRTA1; 179800), in 2 brothers (Karet et al., 1998). The insertion-deletion underlying band-3 Walton consisted of a 13-bp insertion after the first base of amino acid 900 in exon 20. In addition, deletion of 9 bp over the sequence that would have coded for amino acids tyr904 to glu906 of normal band-3 was also present. The net effect was a premature stop codon and deletion of the 11 COOH-terminal amino acids of the protein. The brothers were heterozygous for the mutation. They had thirst, polyuria, and occasional renal colic since childhood and were diagnosed as having distal renal tubular acidosis on the basis of acidosis and hypokalemia at ages 37 and 25 years, respectively. Red cell morphology was normal, but both patients had a tendency to erythremia, a recognized complication of nephrocalcinosis from various causes (Feest et al., 1978). The parents were dead, and there were no known living relatives for study. Toye et al. (2002) demonstrated that the band-3 Walton protein is expressed in the red cell membrane but retained internally in kidney cells.

Quilty et al. (2002) examined the effect of the 11-amino acid C-terminal deletion, which they called 901-stop, on the biosynthesis, folding, and trafficking of AE1 in transfected human embryonic kidney cells. The 901-stop mutation did not effect the folding of AE1, but it did alter its trafficking to the plasma membrane. Coexpression of wildtype and mutant proteins, mimicking the heterozygous state of the patients carrying the mutation (Karet et al., 1998), resulted in heterooligomer formation and impaired trafficking of the wildtype protein to the medial Golgi. Quilty et al. (2002) concluded that the altered trafficking of the mutant protein and its dominant-negative effect could explain both its effect on urine acidification and its dominant inheritance pattern.