New genotypes in Fy(a− b−) individuals: nonsense mutations (Trp to stop) in the 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 chemokine receptor. The Fy(a− b−) phenotype is present in two‐thirds of African‐American Blacks but is rare in Caucasians. In Blacks, the phenotype is due 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‐Fyb or anti‐Fy3. We describe here the molecular analysis of FY in three unrelated Caucasians who were studied because they had strong anti‐Fy3 in their serum. Each was found to have a point mutation that was predicted to change a tryptophan to a premature stop codon in the coding sequence. In one patient (patient 1), the nonsense mutation was at nucleotide 287 of the major transcript in FY A; in another (patient 2), it was at nucleotide 407 in the major transcript of FY B; and in a third (patient 3), it was at nucleotide 408 of the major transcript of FY A.