Molecular basis of the rare gene complex, DIVa(C)-, which encodes four low-prevalence antigens in the Rh blood group system.

BACKGROUND

Over 40 years ago, an unusual Rh phenotype denoted DIVa(C)- was identified in a case of fatal haemolytic disease of the newborn in the third child of Madame Nou. Her RBCs expressed a partial D, weak C and four low-prevalence Rh antigens: Go(a) (RH30), Rh33 (RH33), Riv (RH45) and FPTT (RH50). The purpose of this study was to determine the molecular basis associated with this rare DIVa(C)- complex.

MATERIAL AND METHODS

Blood samples were from three donors previously identified as carrying the DIVa(C)- haplotype. Molecular analyses were performed by standard methods.

RESULTS

The three donors were heterozygous for RHD and RHDDIVa.2, and all carried a compound hybrid allele at the RHCE locus. This hybrid RHCE allele contained exons 2 and 3 from RHDDIVa.2 and exon 5 from RHD [RHCECE-DIVa.2(2-3)-CE-D(5)-CE] and is in cis to RHDDIVa.2. The RHCE allele on the in trans chromosome differs between the donors and is RHCEcE in donor 1, RHCEce (254C, 733G) in donor 2 and RHCE*ce in donor 3.

CONCLUSIONS

The RHDDIVa.2 encodes the Go(a) antigen, whereas the compound hybrid allele most likely encodes Rh33, Riv and FPTT. The weakly expressed C antigen on RBCs with the DIVa(C)- phenotype could be encoded by exons 2 and 3 from RHDDIVa.2 in the compound hybrid. This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. As only one example of anti-Riv has been described, our molecular analysis and findings provide a tool by which to predict Riv expression.