title: RHCE*cE734C allele encodes an altered c antigen and a suppressed E antigen not detected with standard reagents.
abstract: BACKGROUND
  The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression.
  
  
  METHODS
  Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD.
  
  
  RESULTS
  The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected.
  
  
  CONCLUSIONS
  We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
authors.affiliation: Laboratoire d'Hématologie Moléculaire-Etablissement Français du Sang Alpes Méditerranée, UMR 7268-Aix-Marseille Université, Marseille, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Silvy
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barrault
authors.forename: Randall W
authors.initials: RW
authors.lastname: Velliquette
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.forename: Sophie
authors.initials: S
authors.lastname: Simon
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mortelecque
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.forename: France
authors.initials: F
authors.lastname: Noizat-Pirenne
authors.forename: Pascal
authors.initials: P
authors.lastname: Bailly
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournamille
mesh_terms: D001483:Base Sequence; D005838:Genotype; D006386:Hemagglutination Tests; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System