In-frame triplet deletions in RHD alter the D antigen phenotype

Authors

  • Willy A. Flegel,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Nicole I. Eicher,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Andrea Doescher,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Hein Hustinx,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Peter Gowland,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Behrouz Mansouri Taleghani,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Eduard K. Petershofen,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Ursula Bauerfeind,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Manfred Ernst,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Ingeborg Von Zabern,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Hubert Schrezenmeier,

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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  • Franz F. Wagner

    1. From the Department of Transfusion Medicine, University Hospital, Ulm, Germany; the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Blood Transfusion Service (Swiss Red Cross) Bern, Switzerland; DRK Blutspendedienst NSTOB, Institut Oldenburg, Oldenburg, Germany; DRK Blutspendedienst NSTOB, Institut Springe, Springe, Germany; and Biotest AG, Dreieich, Germany.
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Franz F. Wagner, Priv-Doz Dr Med, DRK Blutspendedienst NSTOB, Institut Springe, D-31832 Springe, Germany; e-mail: fwagner@bsd-nstob.de.

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.”

STUDY DESIGN AND 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.

CONCLUSION: 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.

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