The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein

The molecular basis of the three major alleles (Fy(a)/Fy(b)/Fy) of the Duff y (FY) blood group system has recently been established but the Fy(x) pheno type associated with weak expression of the Fy(b) and other FY antigens is poorly understood. In the Fy(x) genes of five unrelated British and Swedish donors with the Fy (a+b+(weak)) phenotype we found two missense mutations predicting amino aci d changes Arg89Cys and Ala100Thr in the FY glycoprotein. The same mutations were found in two Fy(a-b+(weak)) samples from individual s of Swedish and Algerian origin. Their red blood cells showed a marked dec rease in Fy(b), Fy3 and Fy6 expression measured by routine serology and flo w cytometry; The rare FY genotypes Fy(x)Fy(x) and Fy(x)Fy were confirmed by family studies and DIVA sequencing. Screening by allele-specific primer PCR (ASP-PCR) for these mutations among 100 Caucasian and 100 Black random blood donors indicated allele frequenci es of 2.5% and 0%, respectively. Ala100Thr alone was present in 33% of the Caucasians (but none of the Blacks) with no weakening of FY expression. A novel allele at the FY locus associated with the Fy(x) phenotype was stud ied. Mistyping of this weak Fy(b) antigen in clinical transfusion medicine may lead to delayed haemolytic transfusion reactions in immunized patients. A potential role for genomic typing is proposed.