AD(v)-like phenotype is obliterated by A226P in the partial D DBS

BACKGROUND: In D category V types, the RHD exon 5 or parts thereof are repl aced by the corresponding RHCE DNA segments. In D category V types I and II , the amino acid at position 226 is alanine, which is typical of the preval ent RHD allele and is observed in all RHCE alleles encoding the antigen e. A proline at position 226 in RHCE encodes the antigen E. STUDY DESIGN AND METHODS: A blood sample of ccDEe phenotype was referred as suspected D category VI. The RHD nucleotide sequence and the D epitope pat tern were determined. RESULTS: A new partial D, DBS, encoded by an RHD-RHcE(5)-RHD hybrid allele, was found. Although it differed from D-Va type II by an A226P substitution only, it lacked epitopes epD4, epD12, epD17, epD18, and epD22 that were pr esent in D-Va. The 5 ' breakpoint region was located between the deletion i n RHD intron 4 and the first polymorphic nucleotide of DBS exon 5. CONCLUSION: The phenotypes of RHD alleles with gene conversions limited to exon 5 depended critically on the amino acid at position 226. If alanine wa s present at this position, gene conversions involving E233Q led to a D-Va- like phenotype. If proline was present, many additional epitopes were lost, and the phenotype became reminiscent of DFR. The 5 ' breakpoint region is shared by 10 alleles and may represent the most active "hot spot" for gene conversions known in RH.