THE SEROLOGICAL PROFILE AND MOLECULAR-BASIS OF A NEW PARTIAL-D PHENOTYPE, DHR

Background and objectives: The Rh D antigen comprises a mosaic of at l east 30 epitopes expressed on a 30-kD non-glycosylated Rh D polypeptid e. The equivalent Rh CeEe polypeptide expressing the Rh C/c and E/e an tigens differs in only 36 of the 417 amino acid residues. Partial D in dividuals have been described who fail to express a number of D epitop es. Materials and methods: Serologic methods were applied with monoclo nal anti-D to map epitopes on the red cells of a proposita aberrant D typing. Polymerase chain reaction (PCR) and DNA sequencing were also d one. 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 where gene conversion even ts result in the replacement of RHD gene exons with the equivalent RHC E exons the second where point mutation in the RHD gene generates an a mino acid substitution in the Rh D protein. Conclusions: We report her e a new partial D, DHR, where a single point mutation (G to A at nucle otide 686) in exon 5 of the RHD gene results in a conservative amino a cid substitution (Arg229Lys), in the predicted Rh D protein. This resi due is localised on the fourth predicted exofacial loop of the Rh D po lypeptide as determined by hydropathy analysis. This substitution resu lts in the lack of epD 1, 2, 12 and 20 (30 epitope model) and indicate s the involvement of loop 4, and in particular the requirement of Arg( 229), in the expression of these epitopes.