The primary antigens of the Lewis blood group system, Le(a) and Le(b), are not synthesized by red cells but are introduced into the red cell membrane from plasma. The terminology Le(a) and Le(b) is misleading, as these antigens are not allelic. The Le gene, FUT3, encodes an alpha-1,4-L-fucosyltransferase that catalyzes the addition of a fucose residue to the H antigen to produce Le(b) or to the precursor of H to produce Le(a). The presence of H antigen in secretions is governed by the FUT2 gene (182100). Thus, red cells of most H secretors, who have a functional FUT2 enzyme, are Le(a-b+), and those of H nonsecretors (see 182100.0001), who have a nonfunctional FUT2 enzyme, are Le(a+b-). FUT3 can also convert A antigen to ALe(b) and B antigen to BLe(b) (see 110300). About 6% of white people and 25% of black people are homozygous for loss-of-function FUT2 mutations (e.g., 111100.0001) and therefore have Le(a-b-) red cells and lack Lewis substances in their secretions. In Asia, the red cell phenotype Le(a+b+) is common and results from a weak secretor allele in FUT2 (182100.0002). The Le(c) and Le(d) antigens represent precursors of the Le antigens and are present in increased quantities in plasma of Le(a-b-) individuals. The Le(x) and Le(y) antigens are isomers of Le(a) and Le(b), respectively, and are not present in substantial quantities on red cells. Although Le antibodies are relatively common, hemolytic transfusion reactions are rare, and Le antibodies do not cause serious hemolytic disease of the newborn (summary by Daniels, 2002). [from
OMIM]