title: DIIIa and DIII Type 5 are encoded by the same allele and are associated with altered RHCE*ce alleles: clinical implications.
abstract: BACKGROUND
  The partial D phenotype DIIIa was originally reported to be associated with 455A>C in Exon 3, 602C>G in Exon 4, and 667T>G in Exon 5. Other alleles with these changes were subsequently identified and designated DIII Types 5, 6, and 7, as they had additional alterations. The observation that DNA samples associated with the DIIIa phenotype had more changes than those originally reported motivated us to reanalyze the DIIIa probands (BP and DJ) from the original study. We also studied additional DIIIa samples to clarify the RHD background and establish the associated RHCE.
  
  
  METHODS
  Hemagglutination testing was performed by standard methods. RHD and RHCE were analyzed by combinations of polymerase chain reaction-restriction fragment length polymorphism, exon-specific sequencing, cloning, or direct sequencing of Rh-cDNAs.
  
  
  RESULTS
  The RHD alleles from BP, DJ, and 58 additional DIIIa samples had the three reported nucleotide changes as well as 186G>T, 410C>T, and 819G>A. The DIIIa allele was associated with several altered RHCE*ce-alleles, the prominent one being ceS (48C, 733G, 1006T).
  
  
  CONCLUSIONS
  The DIIIa phenotype is associated with six RHD changes, five of which encode amino acid changes, and partial DIIIa and DIII Type 5 are encoded by the same RHD allele. In all samples, RHD*DIIIa was inherited with altered RHCE*ce. Patients with partial DIIIa are at risk for production of alloanti-D, but they are also at risk for alloanti-e, -c, or antibodies to high-prevalence Rh antigens if there is no conventional RHCE*ce in trans. Among 39 patients studied, 16 had alloanti-D and 27 had alloanti-e or anti-hrB.
authors.affiliation: National Molecular Blood Group and Platelet Testing Laboratory, American Red Cross, Philadelphia, Pennsylvania, USA. westhoff@mail.med.upenn.edu
authors.forename: Connie M
authors.initials: CM
authors.lastname: Westhoff
authors.forename: Sunitha
authors.initials: S
authors.lastname: Vege
authors.forename: Christine
authors.initials: C
authors.lastname: Halter-Hipsky
authors.forename: Trina
authors.initials: T
authors.lastname: Whorley
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D012204:Rh-Hr Blood-Group System / Q000235:genetics* / Q000276:immunology
chemical_list: D007518:Isoantibodies; C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen