Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III.
Hereditary spherocytosis (HS) is an inherited haemolytic anaemia, characterized by spheroidal, osmotically fragile red blood cells. This disorder exhibits heterogeneity in terms of both clinical severity and underlying molecular defect. We have studied a South African Cape Coloured individual with severe HS owing to a band 3 deficiency caused by two mutations, occurring in trans, in the band 3 gene: a novel variant that we have designated band 3 Cape Town and a previously described mutation, band 3 Prague III. Analysis of erythrocyte membrane proteins indicated a deficiency of both band 3 and protein 4.2, as well as a decreased functional capacity of band 3 to transport anions. Band 3 Cape Town is defined by a GAG-->AAG point mutation at codon 90, substituting a glutamic acid with a lysine in the cytoplasmic domain of the molecule, while band 3 Prague III is a codon 870 CGG-->TGG point mutation, replacing an arginine with a tryptophan in the transmembrane region of band 3. mRNA is transcribed from both mutant alleles, implying that mutant proteins are synthesized, but are either degraded prior to membrane incorporation or insertion is impaired. We conclude that the combination of these two mutations exacerbated the clinical presentation of the proband.
Bracher
N A
NA
Department of Molecular Medicine and Haematology, South African Institute for Medical Research, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Lyons
C A
CA
Wessels
G
G
Mansvelt
E
E
Coetzer
T L
TL
D000483:Alleles; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D013103:Spherocytosis, Hereditary / Q000235:genetics*
D001457:Anion Exchange Protein 1, Erythrocyte; D012333:RNA, Messenger