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

Transfusion. 2006 Dec;46(12):2156-61. doi: 10.1111/j.1537-2995.2006.01046.x.


Background: The deletion of three adjacent nucleotides in an exon may cause the lack of a single amino acid, while the protein sequence remains otherwise unchanged. Only one such in-frame deletion is known in the two RH genes, represented by the RHCE allele ceBP expressing a "very weak e antigen."

Study design and methods: Blood donor samples were recognized because of discrepant results of D phenotyping. Six samples came from Switzerland and one from Northern Germany. The molecular structures were determined by genomic DNA nucleotide sequencing of RHD.

Results: Two different variant D antigens were explained by RHD alleles harboring one in-frame triplet deletion each. Both single-amino-acid deletions led to partial D phenotypes with weak D antigen expression. Because of their D category V-like phenotypes, the RHD(Arg229del) allele was dubbed DVL-1 and the RHD(Lys235del) allele DVL-2. These in-frame triplet deletions are located in GAGAA or GAAGA repeats of the RHD exon 5.

Conclusion: 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.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Exons
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense
  • Phenotype
  • Rh-Hr Blood-Group System / chemistry
  • Rh-Hr Blood-Group System / genetics*


  • Rh-Hr Blood-Group System
  • Rho(D) antigen