Molecular background of novel silent RHCE alleles
Bach-Nga Pham1, Stéphanie Ramelet, Bénédicte Wibaut
1CNRGS-INSERM U665, Institut National de la Transfusion Sanguine, Paris, France; CHU Lille, Institut d'Hématologie Transfusion, Lille, France; Etablissement Français du Sang, Centre Atlantique, France.
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.
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