Background: Almost all red cells that carry D and/or C antigens also e
xpress the G antigen (Rh12). A study was conducted on the molecular ba
ckground of the G epitope. Study Design and Methods: Two unrelated don
ors with the rare ccDEe, G- phenotype and one donor with the ccEe, Gphenotype were studied. Genomic DNA and cDNA of these donors were stud
ied with polymerase chain reaction, Southern blot, and sequence analys
is, with special focus on exon 2, because it is only in this exon that
there are supposed to be similarities between RHD and the RHC allele,
but not between RHD and the RHc allele. Results: In both ccDEe, G- do
nors, a nucleotide substitution was found in exon 2 of RHD; T307 was r
eplaced by C307, which predicted a Ser-->Pro substitution at amino aci
d position 103 of the D polypeptide. The ccEe, G+ donor carried the co
mplete exon 2 of RHD. Moreover, despite the absence of all known D epi
topes, this donor also carried RHD characteristics in exons 1 to 3 and
exon 9 and further downstream. Conclusion: Ser103, encoded by exon 2
of the RH genes, is involved in G epitope formation.