title: RHCE*ceAG (254C>G, Ala85Gly) is prevalent in blacks, encodes a partial ce-phenotype, and is associated with discordant RHD zygosity.
abstract: BACKGROUND
  RHCE*ceAG has the nucleotide change c.254C>G, which encodes p.Ala85Gly associated with altered expression of e antigen. We analyzed serologic and DNA-based testing data on samples with RHCE*ceAG to determine its effect on antigen expression, linkage with RHD, and its prevalence in African Americans.
  
  
  METHODS
  Serologic testing was performed by standard methods. Genomic DNA was used for polymerase chain reaction-restriction fragment length polymorphism, RH-specific exon sequencing, and RHD zygosity, and Rh-cDNA was sequenced. Samples from 32 individuals referred for serologic problems, 57 patients with sickle cell disease, and 44 donors positive for c.254C>G were investigated. Allele prevalence was determined in random African Americans.
  
  
  RESULTS
  Red blood cells from samples homozygous RHCE*ceAG/ceAG or in trans to RHCE*cE reacted variably with anti-e reagents and 17 samples from the 32 referred patients had alloanti-e in their plasma. The majority of samples with RHCE*ceAG, when tested for RHD zygosity gave discordant results between PstI-RFLP and hybrid box assay. Rare samples with 254C>G had additional allelic changes: one with c.697G (p.233Glu), three with c.733G, 941C (p.245Val, 314Ala), and two with c.307T (p.103Ser) encoding robust C antigen expression in the absence of other C-specific nucleotides. A total of 101 samples with RHCE*ceAG were encountered in 1159 randomly selected African Americans.
  
  
  CONCLUSIONS
  RHCE*ceAG (c.254G, p.85Gly) encodes a partial phenotype and the absence of the high-prevalence antigen RH59 (CEAG). The allele was present in one in 11 African Americans and is most often in cis to a RHD deletion associated with discordant RHD zygosity. To further determine clinical significance, detection of this allele should be part of routine RHCE genotyping in this population.
authors.affiliation: Laboratory of Immunohematology and Genomics.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Westhoff
authors.affiliation: Laboratory of Immunohematology and Genomics.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Vege
authors.affiliation: Laboratory of Immunochemistry, New York Blood Center, New York, New York.
authors.forename: Christine Halter
authors.initials: CH
authors.lastname: Hipsky
authors.affiliation: National Molecular Laboratory, American Red Cross.
authors.forename: Trina
authors.initials: T
authors.lastname: Horn
authors.affiliation: Laboratory of Immunochemistry, New York Blood Center, New York, New York.
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.affiliation: National Molecular Laboratory, American Red Cross.
authors.forename: Jessica
authors.initials: J
authors.lastname: Keller
authors.affiliation: Laboratory of Immunohematology and Genomics.
authors.forename: Randall
authors.initials: R
authors.lastname: Velliquette
authors.affiliation: Laboratory of Immunohematology and Genomics.
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Stella T
authors.initials: ST
authors.lastname: Chou
authors.affiliation: Laboratory of Immunochemistry, New York Blood Center, New York, New York.
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics; D001789:Blood Group Antigens / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D015053:Zygote; D001741:Black or African American
chemical_list: D001789:Blood Group Antigens; D012204:Rh-Hr Blood-Group System