Molecular background of novel silentRHCEalleles

Background The absence of expression of C/c and E/e antigens has been associated with rare variant RHCE alleles, referred to as silent RHCE alleles, classically identified among individuals with a rare D– – or Rhnull phenotype. This work reports on different molecular mechanisms identified in three novel silent RHCE alleles. Study Design and Methods Samples from D– – or Rhnull individuals and their family members, from families for whom Rh phenotype and/or serologic data were unexplained by inheritance of conventional RH alleles, were analyzed. Genomic DNA and transcripts were tested by sequencing analysis. Results The first silent allele was a RHCE*cE allele carrying an intronic IVS3+5G>A mutation. The second was a RHCE*ce allele carrying an intronic IVS7-2A>G mutation, whereas the third was a silent RHCE*ce allele carrying a 5-bp deletion (Nucleotides 679-683) in Exon 5. Conclusion In addition to hybrid alleles and nucleotide deletion, intronic mutations may be associated with the nonexpression of RhCE antigens. Regarding the RH system, silent alleles may not be investigated among D– – or Rhnull individuals only. Rh phenotype and/or serologic data unexplained by inheritance of conventional RH alleles should lead to molecular investigations.