title: Molecular background of D(C)(e) haplotypes within the white population.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Blood Group National Reference Center, Paris, France. pirenne@ints.fr
authors.forename: France
authors.initials: F
authors.lastname: Noizat-Pirenne
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Le Pennec
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mouro
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Rouzaud
authors.forename: Geneviève
authors.initials: G
authors.lastname: Juszczak
authors.forename: Michèle
authors.initials: M
authors.lastname: Roussel
authors.forename: Pierre
authors.initials: P
authors.lastname: Lauroua
authors.forename: Claire
authors.initials: C
authors.lastname: Krause
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouger
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Hélène
authors.initials: H
authors.lastname: Ansart-Pirenne
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D001788:Blood Grouping and Crossmatching; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005796:Genes; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D011110:Polymorphism, Genetic; D011993:Recombinant Fusion Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012204:Rh-Hr Blood-Group System / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D015514:Oncogene Proteins, Fusion; C066468:RHCE protein, human; D011993:Recombinant Fusion Proteins; D012204:Rh-Hr Blood-Group System; C117760:RhD fusion protein, human; C026410:Rho(D) antigen