New RHCE variant alleles encoding the D- - phenotype

Background: Variant alleles that do not produce RhCE antigens are rare. Consequently, they pose a challenge to transfusion when found in alloimmunized patients and make blood units valuable when found in donors.

Study design and methods: Five index cases and their relatives were studied by both serologic and molecular techniques. Genomic DNA was subjected to microarray genotyping, sequencing, exon scanning, and/or copy number determination assays to identify the RHCE allele(s) responsible for their D+ C- c- E- e- (D- -) phenotype.

Results: The five apparent D- - phenotypes were confirmed by molecular methods. Three of them contained unreported RHCE-null alleles, namely, RHCE*Ce-D(3-9)-Ce, RHCE*Ce87_93insT, and RHCE*cE221A.

Conclusion: Molecular analysis of D- - phenotypes allows the identification of new RHCE-null variants. Conversely, detection of described RHCE-null variants facilitates confirmation of D- - phenotypes in patients and donors, helping improve transfusion safety.