Molecular background of novel silent RHCE alleles
Version of Record online: 17 DEC 2012
© 2012 American Association of Blood Banks
Special Issue: Twenty Years since the Cloning of the Blood Group Genes
Volume 53, Issue 11pt2, pages 2990–2999, November 2013
How to Cite
Pham, B.-N., Ramelet, S., Wibaut, B., Juszczak, G., Loukil, C., Dubeaux, I., Gien, D., Kappler-Gratias, S., Rouger, P. and Le Pennec, P.-Y. (2013), Molecular background of novel silent RHCE alleles. Transfusion, 53: 2990–2999. doi: 10.1111/trf.12023
- Issue online: 12 NOV 2013
- Version of Record online: 17 DEC 2012
- Manuscript Accepted: 28 OCT 2012
- Manuscript Revised: 23 OCT 2012
- Manuscript Received: 11 JUL 2012
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.
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.
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.