Nucleotide deletion in RHCE*cE (907delC) is responsible for a D- - haplotype in Hispanics

BACKGROUND: Lack of Cc and Ee expression is associated with either hybrid alleles in which regions of RHCE are replaced by RHD or nucleotide deletion(s) in RHCE. The former have been found as D– – phenotypes, and the latter as Rh_null when accompanied by deletion of RHD. We investigated RH in eight samples, three presenting as D– –, whose c–E– red blood cell (RBC) typing was discordant with the RHCE genotype that predicted c+E+. STUDY DESIGN AND METHODS: Serologic and molecular testing was performed by standard methods. CASES AND RESULTS: RBCs from Patient 1 were D+C?E?c+e+^w but DNA testing predicted E+. RBCs from Patients 2, 3, and 4 typed as D+C?E?c?e? but DNA testing predicted c+E+. All had alloantibodies strongly reactive with all RBCs tested except D– – and Rh_null. Patient 5 had anti‐c and anti‐E but DNA testing predicted she was c+E+. RBCs from three donors typed D+C+E?c?e+ with DNA testing predicting c+E+. All had RHCE*cE with deletion of nucleotide 907C in Exon 6 predicted to cause a premature stop codon at Amino Acid 303 (Leu303Stop). HphI polymerase chain reaction–restriction fragment length polymorphism was used to confirm the deletion and to screen 100 Hispanic, 100 Caucasian, and 100 African American donor samples. One additional example was found. CONCLUSIONS: A novel allele, RHCE*cE 907delC (ISBT provisional designation RHCE*03N.02), silences c and E and in the homozygous state resulted in a D– – phenotype and production of anti‐Rh17. All eight probands were Hispanic. The allele is associated with discrepant molecular typing, with an approximate frequency of 0.005 in Hispanics.