A D<sup>V</sup>‐like phenotype is obliteratedby A226P in the partial D DBS

Wagner, Franz F.; Ernst, M.; Sonneborn, H.‐H.; Flegel, Willy A.

doi:10.1046/j.1537-2995.2001.41081052.x

Cited by 18 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This substitution is hence expected to alter the local structure, but a massive decrease in antigen density (Table 4) and the loss of several epD (Table 5) observed in DCS‐2 suggested more extensive changes important for membrane insertion. DV Type 2 and DBS differ only at position 226 where DV Type 2 carries alanine and DBS proline; this variation causes a considerable change in their epitope patterns 14 . Proline at position 226 also occurs in RhCE as an allelic variation and it determines expression of the E antigen, which is a strongly immunogenic epitope.…”

Section: Discussionmentioning

confidence: 99%

“…DV Type 2 and DBS differ only at position 226 where DV Type 2 carries alanine and DBS proline; this variation causes a considerable change in their epitope patterns. 14 Proline at position 226 also occurs in RhCE as an allelic variation and it determines expression of the E antigen, which is a strongly immunogenic epitope. Therefore, proline at position 226 altered not only RhD but also RhCE protein structure.…”

Section: Discussionmentioning

confidence: 99%

“…DFV was previously recognized in a heterozygous sample in conjunction with a DAR allele in an Afro‐Caribbean individual 11 as well as hemizygous in an individual from Indian descent carrying anti‐D 12 . DCS‐1 was reported in abstract form, 13 when discrepant reactions were observed with monoclonal anti‐D directed to D epitope 6.1 (previously known as epD12) 14‐16 . Furthermore, we found a novel allele , which was termed DCS‐2 due to its phenotypic similarity to DCS‐1.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2007

Self Cite

View full text Add to dashboard Cite

BACKGROUND: RhD and RhCE are structurally related to ammonium transporter proteins, yet their physiologic function remains unclear. Recent threedimensional homology modeling with Escherichia coli AmtB as a template defined a putative transmembraneous channel. Three RhD variants with amino acid substitutions located at the extracellular channel aperture are described. STUDY DESIGN AND METHODS: Blood samples were selected because of serologic abnormalities. RHD, RHCE, and LW nucleotide sequences were determined from genomic DNA. D epitope patterns were established with monoclonal anti-D panels. Threedimensional Rh structures were calculated by alignment to AmtB. RESULTS:The RHD allele DCS-1 was found to carry the two amino acid substitutions F223V (667T > G) and A226P (676G > C) caused by missense mutations in RHD exon 5. This study compared DCS-1 with the D variants DFV (F223V) and DCS-2 (A226P), harboring solely one or the other of the two substitutions. All three D variants were associated with a cDE haplotype. The antigen densities were approximately 3000 D antigens per red blood cell for DCS-1, 800 for DCS-2, and 9300 for DFV. DCS-1 and DCS-2 were partial D, because they lacked distinct epitopes. DFV presented as an almost normal D phenotype; the sample contained allo-anti-LW a . The D w antigen was absent from DCS-1, DFV, and DAU-4, but expressed by DAU-5. CONCLUSION: DCS-1, DCS-2, and DFV carry amino acid substitutions at the extracellular vestibule, visualized by 3-dimensional modeling. Proline at position 226 greatly influenced the D antigen density and may reduce the RhD membrane integration. Although the F223V substitution is regarded as the initial event in the evolution of the weak D Type 4 cluster, the current DFV allele probably evolved independently, as evident from different RHCE haplotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, there are examples of similar alleles that arose from independent gene conversion events within the Eurasian D cluster. Some DV alleles appear to have been caused by random or independent molecular events, and for these reasons, the DV group of partial D is not defined as a cluster 70.…”

Section: Rhd Phylogenymentioning

confidence: 99%

Molecular genetics and clinical applications for RH

Flegel

2011

Transfusion and Apheresis Science

Self Cite

148

182

View full text Add to dashboard Cite

Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of general genetic mechanisms. For clinical purposes, genetic diagnostics of Rhesus antigens will improve the cost-effective development of transfusion medicine.

show abstract

“…The protein segment encoded RH exon 5 may be an important determinant of the D as well as CE antigen expression. Many clinically relevant variants of RHD exon 5 are known, 31 and it was recently screened systematically 32 . The example of ceCF fits well into the group of clinically relevant RhCE protein variants with RHCE exon 5 mutations including VS+ alleles (Fig.…”

Section: Discussionmentioning

confidence: 74%