In‐frame triplet deletions in RHD alter the D antigen phenotype

Abstract

Partial D may be caused by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL types are adjacent to the extracellular loop 4, which constitutes one of the most immunogenic parts of the D antigen. These RhD protein segments are also altered in all DV, which may explain the similarity in phenotype. At the nucleotide level, the triplet deletions may have resulted from replication slippage. A total of nine amino acid positions in an Rhesus protein may be affected by this mechanism.

RHCE alleles detected after weak and/or discrepant results in automated Rh blood grouping of blood donors in Northern Germany

“…This mechanism has been shown before to occur in RHCE 39 and RHD 40 and had been proposed to be triggered by the DNA motifs GAGAA or GAAGA and complementary TTCTC or TCTTC. 40 Based on this assumption, nine possible amino acid positions for the occurrence of in-frame triplet deletions had been suggested. The newly found RHCE allele caused by an in-frame triplet deletion at amino acid position 27 confirmed the predicted position (Fig.…”

DCS‐1, DCS‐2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule

“…Ethylenediaminetetraacetate‐ or citrate‐anticoagulated blood samples were collected in the Czech Republic and Germany. Rh phenotypes and D epitopes were determined by hemagglutination in gel matrix test (DiaMed, Cressier sur Morat, Switzerland) 17 . If not stated otherwise, monoclonal anti‐D came from the International Workshops on Monoclonal Antibodies Against Human Red Blood Cells and Related Antigens in Nantes 1996 and in Paris 2001.…”

Local sequence determinants of two in-frame triplet deletion/duplication hotspots in the RHD/RHCEgenes

“…As pointed out by the original authors, this duplication could have resulted from either a duplication of c.74-76TTC or c.75_77TCT. These authors emphasized the importance of a DNA motif (i.e., TTCTC that was identified by analogy to previously reported deletion-predisposing DNA motifs in the RHD gene [9]) in generating this duplication but did not provide a model to explain how this duplication could have been generated. Given that the sequence tract in question is prone to replication slippage, we surmised that this duplication might also be explicable in terms of such a mechanism.…”

“…The second hotspot refers to a 63-bp region of exon 5 in the RHD and RHCE genes, in which four in-frame triplet deletions (c.644_646delTCT [3], c.684_686delGAG, and c.705_707delAGA [9] in RHD ; c.685_687delAGA [10] in RHCE ) were reported (Figure 2). Several distinct DNA repeats or motifs (e.g., GAGAA and GAAGA) have previously been implicated in the generation of three of these four variants [9].…”

“…Several distinct DNA repeats or motifs (e.g., GAGAA and GAAGA) have previously been implicated in the generation of three of these four variants [9]. A comparative evaluation of the four variants led us to propose a consensus motif RAGAA (R = A or G) (Figure 2).…”