New genotypes in Fy(a-b-) individuals: nonsense mutations (Trp to stop) inthe coding sequence of either FY A or FY B

Duffy blood group antigens are carried on a glycoprotein that is predicted to pass through the erythrocyte membrane seven times and is a promiscuous c hemokine receptor. The Fy(a-b-) phenotype is present in two-thirds of Afric an-American Blacks but is rare in Caucasians. In Blacks, the phenotype is d ue to a non-functional GATA-1 motif in the FY B, which silences the gene in erythrocytes but not in other tissues, and these patients do not generally make anti-Fy(b) or anti-Fy3. We describe here the molecular analysis of FY in three unrelated Caucasians who were studied because they had strong ant i-Fy3 in their serum. Each was found to have a point mutation that was pred icted to change a tryptophan to a premature stop codon in the coding sequen ce. In one patient (patient 1), the nonsense mutation was at nucleotide 387 of the major transcript, in FY A; in another (patient 2), it was at nucleo tide 407 in the major transcript of FY B; and in a third (patient 2), it wa s at nucleotide 408 of the major transcript; of FY A.