BACKGROUND: In the Rh blood group system, variant RhD and RhCE express several partial antigens. We investigated RH in samples with partial DIVa that demonstrated weak and variable reactivity with anti‐C. STUDY DESIGN AND METHODS: Standard hemagglutination techniques, polymerase chain reaction–based assays, and RH sequencing were used. RESULTS: DNA analysis showed that six red blood cell (RBC) samples with weak and inconsistent reactivity with anti‐C lacked RHCE*C, but all had RHD*DIVa, which encodes partial D and Goa. We then tested RBCs from 19 Go(a+) cryopreserved samples (confirmed to have RHD*DIVa) with four anti‐C and observed weak variable reactions. RHCE genotyping found all but one of the samples with RHD*DIVa also had RHCE nt 48G>C and 1025C>T, named RHCE*ceTI. Lookback of samples referred for workup and found to have either allele revealed 47 of 55 had both RHD*DIVa and RHCE*ceTI, four had RHD*DIVa without RHCE*ceTI, and four had RHCE*ceTI without RHD*DIVa. Alloanti‐c was found in a patient with c+ RBCs and RHCE*ceTI in trans to RHCE*Ce, and alloanti‐e was found in a patient with e+ RBC and RHCE*ceTI in trans to RHCE*cE. RHD*DIVa in trans to RHD erroneously tested as RHD hemizygous. CONCLUSIONS: RHD*DIVa and RHCE*ceTI almost always, but not invariably, travel together. This haplotype is found in people of African ancestry and the RBCs can demonstrate aberrant reactivity with anti‐C. RHCE*ceTI encodes partial c and e antigens. We confirm that RHD zygosity assays are unreliable in samples with RHD*DIVa.

Background RHCE*ceMO has nucleotide changes 48G>C and 667G>T, which encode, respectively, 16Cys and 223Phe associated with altered expression of e antigen. RHD*DAU0 has nt1136C>T, which encodes 379Met associated with normal levels of D. We compiled serologic and DNA testing data on samples with RHCE*ceMO to determine the RBC antigen expression, antibody specificity, RHD association, and the prevalence in African-Americans. Methods Serologic testing was performed by standard methods. Genomic DNA was used for PCR-RFLP and RH- exon sequencing, and for some, Rh-cDNA was sequenced. Seventy-seven (50 donor and 27 patient) samples with RHCE*ceMO were studied, and 350 African-Americans were screened for allele prevalence. Results RBCs from RHCE*ceMO homozygotes (or heterozygotes with RHCE*cE in trans) were weakly or non-reactive with some anti-e , and were non-reactive with polyclonal anti-hrS and anti-hrB. Twenty-three transfused patients homozygous for RHCE*ceMO/ceMO or with RHCE*ceMO in trans to RHCE*cE or *ce had allo anti-e, anti-f, anti-hrS/hrB, or an antibody to a high prevalence Rh antigen. Three patients with allo-anti-c had RHCE*ceMO in trans to RHCE*Ce. RHD*DAU0 was present in 30% of African-Americans tested and in 69 of 77 (90%) of samples with RHCE*ceMO. Conclusions RHCE*ceMO encodes partial e, as previously reported, and also encodes partial c, a hrS– and hrB– phenotype, and the absence of a high prevalence antigen (RH61). The antibody in transfused patients depended on the RHCE allele in trans. RHCE*ceMO was present in 1 in 50 African-Americans with an allele frequency of 0.01, is often linked to RHD*DAU0, and is potentially of clinical significance for transfusion.

BACKGROUND Mutation in the KLF1 gene is the cause of the In(Lu) (Inhibitor of Lutheran) Lu(a–b–) phenotype and more than 60 alleles have been associated with this phenotype. Here we describe findings from investigation of seven cases: six presenting with a Lu(a–b–) phenotype including the historical index case and one referred from a patient with chronic anemia. STUDY DESIGN AND METHODS Serologic testing was by standard methods. DNA testing included amplification and sequencing of KLF1 and LU coding regions. A StuI polymerase chain reaction–restriction fragment length polymorphism was designed to target c.304T>C in KLF1. RESULTS Five different KLF1 alleles were identified. Three are new: KLF1*90A (p.Trp30Ter), KLF*911A (p.Thr304Lys), and KLF1*304C,318G (p. Ser102Pro, Tyr106Ter) present in two unrelated individuals. Two, including the index case, had c.954dupG (p.Arg319Glufs*34), that is, KLF1*BGM06. The child with unexplained anemia had c.973G>A (p.Glu325Lys), associated with congenital dyserythropoietic anemia. The common c.304T>C was found in two of the seven samples investigated and in 60 of 100 blood donors. CONCLUSION Mutations in KLF1 are pleiotropic and although most are benign, others are associated with hematologic abnormalities. We report three new KLF1 alleles associated with benign In(Lu) and document both the molecular basis of the original In(Lu) phenotype using a frozen sample stored for more than 50 years and the cause of unexplained anemia in a child. We also confirm previous observations that c.304C (p.102Pro) is not, by itself, associated with an In(Lu) phenotype in donors self‐identified as U.S. minorities.

JK*A (561C>A) is associated with a Kidd-null phenotype in this African American family. The allele was present in approximately one in 168 Brazilian blacks, suggesting that detection of this allele is important to avoid false-positive prediction of Jk(a) status in this population.