Background and objectives: The Rh D antigen comprises a mosaic of at least 30 epitopes expressed on a 30-kD non-glycosylated Rh D polypeptide. The equivalent Rh CeEe polypeptide expressing the Rh C/c and E/e antigens differs in only 36 of the 417 amino acid residues. Partial D individuals have been described who fail to express a number of D epitopes.
Materials and methods: Serologic methods were applied with monoclonal anti-D to map epitopes on the red cells of a proposita aberrant D typing. Polymerase chain reaction (PCR) and DNA sequencing were also done.
Results: DNA sequence analysis derived by RT-PCR using total RNA isolated from peripheral blood of this person suggests two mechanisms for the genetic basis of this variants: one here gene conversion events result in the replacement of RHD gene exons with the equivalent RHCE exons; the second where point mutation in the RHD gene generates an amino acid substitution in the Rh D protein.
Conclusions: We report here a new partial D, DHR, where a single point mutation (G to A at nucleotide 686) in exon 5 of the RHD gene results in a conservative amino acid substitution (Arg229Lys), in the predicted Rh D protein. This residue is localised on the fourth predicted exofacial loop of the Rh D polypeptide as determined by hydropathy analysis. This substitution results in the lack of epD 1, 2, 12 and 20 (30 epitope model) and indicates the involvement of loop 4, and in particular the requirement of Arg229, in the expression of these epitopes.