title: In-frame triplet deletions in RHD alter the D antigen phenotype.
abstract: BACKGROUND
  The deletion of three adjacent nucleotides in an exon may cause the lack of a single amino acid, while the protein sequence remains otherwise unchanged. Only one such in-frame deletion is known in the two RH genes, represented by the RHCE allele ceBP expressing a "very weak e antigen."
  
  
  METHODS
  Blood donor samples were recognized because of discrepant results of D phenotyping. Six samples came from Switzerland and one from Northern Germany. The molecular structures were determined by genomic DNA nucleotide sequencing of RHD.
  
  
  RESULTS
  Two different variant D antigens were explained by RHD alleles harboring one in-frame triplet deletion each. Both single-amino-acid deletions led to partial D phenotypes with weak D antigen expression. Because of their D category V-like phenotypes, the RHD(Arg229del) allele was dubbed DVL-1 and the RHD(Lys235del) allele DVL-2. These in-frame triplet deletions are located in GAGAA or GAAGA repeats of the RHD exon 5.
  
  
  CONCLUSIONS
  Partial D may be caused by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL types are adjacent to the extracellular loop 4, which constitutes one of the most immunogenic parts of the D antigen. These RhD protein segments are also altered in all DV, which may explain the similarity in phenotype. At the nucleotide level, the triplet deletions may have resulted from replication slippage. A total of nine amino acid positions in an Rhesus protein may be affected by this mechanism.
authors.affiliation: Department of Transfusion Medicine, University Hospital, Ulm, Germany.
authors.forename: Willy A
authors.initials: WA
authors.lastname: Flegel
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Eicher
authors.forename: Andrea
authors.initials: A
authors.lastname: Doescher
authors.forename: Hein
authors.initials: H
authors.lastname: Hustinx
authors.forename: Peter
authors.initials: P
authors.lastname: Gowland
authors.forename: Behrouz
authors.initials: B
authors.lastname: Mansouri Taleghani
authors.forename: Eduard K
authors.initials: EK
authors.lastname: Petershofen
authors.forename: Ursula
authors.initials: U
authors.lastname: Bauerfeind
authors.forename: Manfred
authors.initials: M
authors.lastname: Ernst
authors.forename: Ingeborg
authors.initials: I
authors.lastname: von Zabern
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Franz F
authors.initials: FF
authors.lastname: Wagner
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D012204:Rh-Hr Blood-Group System / Q000737:chemistry / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen