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In‐frame triplet deletions in RHD alter the D antigen phenotype
Author(s) -
Flegel Willy A.,
Eicher Nicole I.,
Doescher Andrea,
Hustinx Hein,
Gowland Peter,
Mansouri Taleghani Behrouz,
Petershofen Eduard K.,
Bauerfeind Ursula,
Ernst Manfred,
Von Zabern Ingeborg,
Schrezenmeier Hubert,
Wagner Franz F.
Publication year - 2006
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2006.01046.x
Subject(s) - phenotype , antigen , genetics , frame (networking) , biology , medicine , gene , computer science , telecommunications
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.