TOTAL ABSENCE OF PROTEIN-4.2 AND PARTIAL DEFICIENCY OF BAND-3 IN HEREDITARY SPHEROCYTOSIS

Unlike previously reported cases with total protein 4.2 deficiency due to mutations in the EPB42 gene, we describe a total deficiency in pro tein 4.2 with normal EPB42 alleles, Hereditary spherocytosis (HS) was observed in a Japanese woman (unsplenectomized) and her daughter (sple nectomized), The mother showed a partial deficiency in band 3 and a pr oportional reduction in protein 4.2, She was heterozygous for a novel allele of the EPB3 gene, allele Okinawa, which contains the two mutati ons that define the Memphis II polymorphism (K56E, AAG --> GAG, and P8 54L, CCG --> CTG) and, additionally, the mutation: G714R, GGG --> AGG, located in a highly conserved position of transmembrane segment 9, Th e latter change was responsible for HS, In trans to allele Okinawa, th e daughter displayed allele Fukuoka: G13OR, GGA --> AGA, an allele kno wn to alter the binding of protein 4.2 to band 3. The daughter present ed with a more pronounced decrease of band 3, and lacked protein 4.2, resulting in aggravated haemolytic features. Although the father was n ot available for study, heterozygosity for allele Fukuoka has been doc umented in another individual who showed no clinical or haematological signs, and a normal content of band 3. We suggest that band 3 Okinawa binds virtually all the protein 4.2 in red cell precursors, band 3 Fu kuoka being unable to do so, and that the impossibility of band 3 Okin awa incorporation into the membrane leads to degradation of the band 3 Okinawa protein 4.2 complex. In contrast, band 3 Fukuoka, free of bou nd protein 4.2, could then incorporate normally into the bilayer. Thus , protein 4.2 would not appear in the daughter's red cell membrane.