DUPLICATION OF 10 NUCLEOTIDES IN THE ERYTHROID BAND 3 (AE1) GENE IN AKINDRED WITH HEREDITARY SPHEROCYTOSIS AND BAND-3 PROTEIN-DEFICIENCY (BAND-3(PRAGUE))

We describe a duplication of 10 nucleotides (2,455-2,464) in the band 3 gene in a kindred with autosomal dominant hereditary spherocytosis a nd a partial deficiency of the band 3 protein that is reflected by dec reased rate of transmembrane sulfate flux and decreased density of int ramembrane particles. The mutant allele potentially encodes an abnorma l band 3 protein with a 3.5-kD COOH-terminal truncation; however, we d id not detect the mutant protein in the membrane of mature red blood c ells. Since the mRNA levels for the mutant and normal alleles are simi lar and since the band 3 content is the same in the light and dense re d cell fractions, we conclude that the mutant band 3 is either not ins erted into the plasma membrane or lost from the membrane prior to the release of red blood cells into circulation. We further show that the decrease in band 3 content principally involves the dimeric laterally and rotationally mobile fraction of the band 3 protein, while the late rally immobile and rotationally restricted band 3 fraction is left ess entially intact. We propose that the decreased density of intramembran e particles decreases the stability of the membrane lipid bilayer and causes release of lipid microvesicles that leads to surface area defic iency and spherocytosis.