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P36
A Novel RhD Variant
Author(s) -
Tilley L.,
Bullock T.,
Mason R.,
Poole J.,
Daniels G.
Publication year - 2006
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/j.1365-3148.2006.00694_36.x
Subject(s) - phenotype , exon , epitope , gene , genetics , mutation , biology , microbiology and biotechnology , antigen
Variants of the RhD antigen are often categorised into weak D and partial D phenotypes, although the distinction between the two groups is unclear. One frequently used definition is the ability to make alloanti‐D in partial D, but not in weak D phenotypes, however some phenotypes characterised as weak D are now known to be associated with alloanti‐D production. On a molecular level, weak D phenotypes usually possess RHD mutations encoding amino acid subsitutions within the cytoplasmic or membrane spanning regions of RhD, whilst partial D phenotypes result from changes in the extracellular loops. Thus, weak D red cells could be regarded as having all epitopes of D, but expressed weakly, whilst partial D cells lack some D epitopes. We investigated the red cells of a black pregnant woman because of aberrant reactions obtained in routine D typing, in order to decide if prophylactic anti‐D should be given. Methods Routine anti‐D sera and a reagent anti‐D panel were tested serologically by their recommended techniques. Genomic DNA was extracted from whole blood and subjected to sequencing of exons 1 to 9 of the RHD gene. Results and treatment The Rh phenotype of the patient was C‐ c+, E‐, e+, V+, VS+. Anti‐D reagents gave variable reactions and a novel pattern of reactions was seen with an anti‐D panel. Sequencing analysis revealed a single G>A mutation at position 490, within exon 4 of the RHD gene, resulting in an Aspartate to Asparagine change at position 164 of the RhD protein (D164N). This appears to be a novel RHD mutation. The patient received prophylactic anti‐D antenatally and at delivery. The maternal antibody screen and Kliehauer screen were negative and she delivered a full term D+ DAT negative infant. Conclusions A novel D variant has been identified with an D164N mutation, predicted to lie within the third extracellular loop of the RhD protein. We propose to call this D variant DDN. The molecular basis of this novel phenotype suggests that this could be categorised as a partial D , as the mutation results in a loss of D epitopes. This would be expected to result in the ability to produce alloanti‐D although alloanti‐D production was not reported in this case.