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

• Published in: Vox sanguinis 2010-04, Vol.98 (3 Pt 1), p.e263-e268
• Main Authors: Hue-Roye, K, O'Shea, K, Gillett, R, Wadsworth, L D, Hume, H, Barnes, J, Kinney, J, Hodgins, K, Fuchisawa, A, Lomas-Francis, C, Reid, M
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0042-9007; 1423-0410
• DOI: 10.1111/j.1423-0410.2009.01277.x

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. 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. 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. 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.