The low prevalence Rh antigen Be(a) (Rh36) is associated with RHCE*ce 662C>G in exon 5, which is predicted to encode Rhce 221Arg

Vox Sang. 2010 Apr;98(3 Pt 1):e263-8. doi: 10.1111/j.1423-0410.2009.01277.x. Epub 2009 Nov 23.


Background and objectives: The low prevalence antigen, Be(a), is produced by a complex that also produces weak c, e and f (ce). We report here the molecular basis associated with Be(a) antigen expression.

Materials and methods: Peripheral blood samples from four Be(a+) probands were tested. Haemagglutination, gDNA extraction, PCR-based assays, reticulocyte RNA isolation, Rh-cDNA analyses, and sequencing were performed by standard procedures.

Results: RBCs from Probands 1 and 3 were D-C-E-c+e+, and from Probands 2 and 4 were D+C+E-c+(W)e+. In proband 1, cDNA sequencing of RHCE revealed heterozygosity of nucleotide (nt) 662C/G in exon 5 of RHCE*ce. No other nucleotide changes were observed. As the 662C>G nucleotide change ablates a MscI restriction enzyme cleavage site, PCR-RFLP analysis was performed and the RHCE*ce nt 662C/G heterozygosity was detected on gDNA from the four probands and two children from both Proband 3 and Proband 4.

Conclusion: The low prevalence Rh antigen, Be(a), is associated with a single nucleotide change in exon 5 of RHCE*ce; that of 662C>G and this change is predicted to alter proline at amino acid position 221 of Rhce to arginine. The fundamental differences in the properties of these two amino acids may impose a steric and/or charge-related effect on the protein, and thereby provide an explanation for the weakened expression of c, e and f (ce) antigens in the Be(a) phenotype.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Substitution
  • DNA, Complementary / genetics
  • Erythroblastosis, Fetal / genetics*
  • Exons / genetics*
  • Female
  • Genotype
  • Humans
  • Infant, Newborn
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Rh-Hr Blood-Group System / genetics*
  • Sequence Analysis, DNA


  • DNA, Complementary
  • RHCE protein, human
  • Rh-Hr Blood-Group System