Background: The red blood cells (RBCs) of a patient, known to have the probable DC(W)(e)/D-- phenotype, typed as D(W)- and Rh32- but were unexpectedly agglutinated by an anti-D(W)/Rh32 serum. The reactivity suggested that the RBCs carried a novel antigen and that the molecular background of this DC(W)(e)/D-- phenotype might be different from those reported. The purpose of this study was to determine the molecular basis of the Rh phenotype.
Study design and methods: Samples were obtained for family studies. Standard hemagglutination methods were used. RH mRNA transcripts were isolated by reverse transcription-polymerase chain reaction and sequenced.
Results: Sequence analysis revealed that the probond had three different RH transcripts: a normal RHD and two different hybrid transcripts from the RHCE locus, a RHCE-D hybrid with exon 1 from RHCE associated with the D-- haplotype, and a new RHCE-D hybrid. In this new hybrid, exons 1 to 5 are RHCe-specific and exons 6 to 10 correspond to RHD. The C(W) antigen is also encoded by this hybrid gene. Family studies confirmed that the new RHCE-D hybrid is linked in cis to conventional RHD.
Conclusion: A new RHCE-D structure is associated with altered expression of C and e antigens in this family and the generation of a novel low-prevalence antigen (CENR).