Molecular background of D(C)(e) haplotypes within the white population

Transfusion. 2002 May;42(5):627-33. doi: 10.1046/j.1537-2995.2002.00097.x.


Background: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e.

Study design and methods: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low-frequency antigens of the Rh (RH) system and other non-Rh low-frequency antigens. Neither Hor+, Mol+ nor Hor+, Mol- RBCs expressed the V (RH10), VS (RH20), and/or Rh32 (RH32) low-frequency antigens. These results suggested that Hor+, Mol+ variants expressed Rh33 (RH33 or Har) and FPTT (RH50), whereas Hor+, Mol- variants might express an undefined low-frequency antigen. Further serologic and molecular analyses were performed.

Results: Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe-D(5)-Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so-called RHCeVA allele). The presence of exon 5RHD resulted in several amino acid alterations predicted in the external loop 4 of the CeVA polypeptide. Molecular analysis of Hor+, Mol- variants revealed the presence of a new RHCe allele characterized by a single point mutation C340T within exon 3 (the so-called RHCeMA allele), resulting in a R114W substitution predicted on the external loop 2 of the CeMA polypeptide. A serologic study showed a different pattern of reactivity with C and e MoAbs.

Conclusion: Two types of mutations resulted in amino acid substitutions predicted in external loops 4 and 2, respectively, which altered both the C and e reactivity, and indicated conformation changes or defective interaction between nonadjacent loops of the Ce polypeptide. Serologic analysis showed that together with Hor and Mol sera testing, the use of different C and e MoAbs could help to identify these variants within the white population.

Publication types

  • Comparative Study

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Antibodies, Monoclonal / immunology
  • Blood Grouping and Crossmatching
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Gene Expression Regulation
  • Genes
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics*
  • Glycoproteins / immunology
  • Haplotypes / genetics*
  • Humans
  • Male
  • Models, Molecular
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / immunology
  • Pedigree
  • Polymorphism, Genetic
  • Recombinant Fusion Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rh-Hr Blood-Group System / biosynthesis
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology
  • White People / genetics*


  • Antibodies, Monoclonal
  • Glycoproteins
  • Oncogene Proteins, Fusion
  • RHCE protein, human
  • Recombinant Fusion Proteins
  • Rh-Hr Blood-Group System
  • RhD fusion protein, human
  • Rho(D) antigen