title: Duplication of 10 nucleotides in the erythroid band 3 (AE1) gene in a kindred with hereditary spherocytosis and band 3 protein deficiency (band 3PRAGUE).
abstract: We describe a duplication of 10 nucleotides (2,455-2,464) in the band 3 gene in a kindred with autosomal dominant hereditary spherocytosis and a partial deficiency of the band 3 protein that is reflected by decreased rate of transmembrane sulfate flux and decreased density of intramembrane particles. The mutant allele potentially encodes an abnormal band 3 protein with a 3.5-kD COOH-terminal truncation; however, we did not detect the mutant protein in the membrane of mature red blood cells. Since the mRNA levels for the mutant and normal alleles are similar and since the band 3 content is the same in the light and dense red cell fractions, we conclude that the mutant band 3 is either not inserted 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 laterally immobile and rotationally restricted band 3 fraction is left essentially intact. We propose that the decreased density of intramembrane particles decreases the stability of the membrane lipid bilayer and causes release of lipid microvesicles that leads to surface area deficiency and spherocytosis.
authors.affiliation: Department of Biomedical Research, St. Elizabeth's Hospital, Boston, MA 02135.
authors.forename: P
authors.initials: P
authors.lastname: Jarolim
authors.forename: H L
authors.initials: HL
authors.lastname: Rubin
authors.forename: S C
authors.initials: SC
authors.lastname: Liu
authors.forename: M R
authors.initials: MR
authors.lastname: Cho
authors.forename: V
authors.initials: V
authors.lastname: Brabec
authors.forename: L H
authors.initials: LH
authors.lastname: Derick
authors.forename: S J
authors.initials: SJ
authors.lastname: Yi
authors.forename: S T
authors.initials: ST
authors.lastname: Saad
authors.forename: S
authors.initials: S
authors.lastname: Alper
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency* / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D001663:Bilirubin / Q000097:blood; D004247:DNA / Q000097:blood; D017931:DNA Primers; D004910:Erythrocyte Membrane / Q000648:ultrastructure; D005260:Female; D005614:Freeze Fracturing; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D017931:DNA Primers; D006454:Hemoglobins; D012333:RNA, Messenger; D004247:DNA; D001663:Bilirubin