Heterogeneous molecular background of the weak C, VS+, hr B-, Hr B- phenotype in black persons.

ABSTRACT

BACKGROUND: The rare Hr(B)- phenotype is encoded by the (C)ce(s) haplotype when present at the homozygous state. This haplotype contains two altered genes a hybrid RHD-CE-D(s) gene segregated with a ce(s) allele of RHCE (733C>G and 1006G>T substitutions in Exon 5 and Exon 7 respectively). The aim of this study was to further investigate the molecular background of the (C)ce(s) haplotype. STUDY DESIGN AND METHODS: Twelve individuals with depressed C and/or depressed e phenotype were selected from their genomic DNA analysis showing both 733C>G and 1006G>T substitutions. Phenotypic expression of low- and high-prevalence Rh antigens was studied. Complete sequences of RHD and RHCE transcripts were analyzed when obtained. RESULTS: A new hybrid RHD-CE-D(s) gene (Exons 1 and 2; complete Exon 3; Exons 8, 9, and 10 from RHD; and Exons 4 through 7 from RHCE) segregated with a ce(s) allele, which genomic organization was almost identical to that of the classical (C)ce(s) haplotype, is described. The two different (C)ce(s) haplotypes encoded two different patterns of Rh antigen expression. Although both encoded weak e, VS, and did not produce D, V, hr(B), or Hr(B) antigens, the new haplotype encoded a much weaker C antigen and red blood cells lacked expression of Rh42, in contrast to the classic (C)ce(s) haplotype. CONCLUSION: The study showed the heterogeneity of the molecular background of the weak C, VS+, hr(B)-, Hr(B)- phenotype in the black population. The screening of blood donors in this population for hr(B)- or Hr(B)- phenotype should implement the molecular characterization of Rh genes.