First example of an FY*01 allele associated with weakened expression of Fya on red blood cells.

Duffy antigens are important in immunohematology. the reference allele for the Duffy gene (FY) is FY02, which encodes Fy(b). An A>G single nucleotide polymorphism (SNP) at coding nucleotide (c.) 125 in exon 2 defines the FY01 allele, which encodes the antithetical Fy(a). A C>T SNP at c.265 in the FY02 allele is associated with weakening of Fy(b) expression on red blood cells (R BCs) (called Fy(x)). until recently, this latter change had not been described on a FY01 background allele. Phenotype-matched units were desired for a multi-transfused Vietnamese fetus with α-thalassemia. Genotyping of the fetus using a microarray assay that interrogates three SNPs (c.1-67, c.125, and c.265) in FY yielded indeterminate results for the predicted Duffy phenotype. Genomic sequencing of FY exon 2 showed that the fetal sample had one wild-type FY01 allele and one new FY01 allele with the c.265C>T SNP, which until recently had only been found on the FY02 allele. Genotyping performed on samples from the proband's parents indicated that the father had the same FY genotype as the fetus. Flow cytometry, which has been previously demonstrated as a useful method to study antigen strength on cells, was used to determine if this new FY01 allele was associated with reduced Fy(a) expression on the father's RBCs. Median fluorescence intensity of the father's RBCs (after incubation with anti-FY(a) and fluorescein-labeled anti-IgG) was similar to known FY01 heterozygotes. and significantly weaker than known FY01 homozygotes. In conclusion, the fetus and father both had one normal FY01 allele and one new FY01W.01, is associated with weakened expression of Fy(a) on RBCs.