In-frame triplet deletions in RHD alter the D antigen phenotype.
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.
Flegel
Willy A
WA
Department of Transfusion Medicine, University Hospital, Ulm, Germany.
Eicher
Nicole I
NI
Doescher
Andrea
A
Hustinx
Hein
H
Gowland
Peter
P
Mansouri Taleghani
Behrouz
B
Petershofen
Eduard K
EK
Bauerfeind
Ursula
U
Ernst
Manfred
M
von Zabern
Ingeborg
I
Schrezenmeier
Hubert
H
Wagner
Franz F
FF
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*
D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen