Weak D type 1.1 exemplifies another complexity in weak D genotyping.
BACKGROUND
Weak D expression is caused by a large number of RHD alleles. Increasingly recommendations for D+ or D- transfusions are based on polymerase chain reaction (PCR) identification of certain RHD alleles. Possible sources of error are rare D variants that are inadvertently carrying known polymorphisms of frequent weak D types.


METHODS
Weak D donors were checked by direct column agglutination. In donors with unusually weak expression of D, the molecular weak D type was determined by weak D PCR and nucleotide sequencing. The serologic profile of a weak D type 1 variant was determined by agglutination serology and flow cytometry.


RESULTS
Several donors in whom direct agglutination barely revealed any D expression were shown to carry the new RHD(L18V,V270G) allele dubbed weak D type 1.1. Initially, such donors had been mistyped as weak D type 1 by PCR. In a systematic study, weak D type 1.1 was shown to be present in 7 of 23 donors with very weak D expression who all lived in a restricted area of Northern Germany. Although weak D type 1.1 was typed D- or barely D+ by direct agglutination, it was easily detected by antiglobulin technique and was shown to carry about 600 antigens D per red blood cell.


CONCLUSIONS
The observation of weak D type 1.1 with its distinct phenotype pinpointed to two general problems of current RHD genotyping strategies: Mistyping of alleles with additional mutations and striking geographic variation of the allele distributions.
Doescher
Andrea
A
DRK Blutspendedienst NSTOB, Oldenburg Institute, Oldenburg, Germany.
Flegel
Willy A
WA
Petershofen
Eduard K
EK
Bauerfeind
Ursula
U
Wagner
Franz F
FF
D000017:ABO Blood-Group System / Q000032:analysis; D000483:Alleles; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D001782:Blood Donors; D001788:Blood Grouping and Crossmatching / Q000379:methods; D016000:Cluster Analysis; D003298:Coombs Test; D004910:Erythrocyte Membrane / Q000276:immunology; D005006:Ethnicity / Q000235:genetics*; D005188:False Negative Reactions; D005434:Flow Cytometry; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D006386:Hemagglutination Tests; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008958:Models, Molecular; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012204:Rh-Hr Blood-Group System / Q000032:analysis / Q000145:classification / Q000235:genetics* / Q000276:immunology; D018029:Rho(D) Immune Globulin; D017422:Sequence Analysis, DNA
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D007518:Isoantibodies; C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen