Weak A phenotypes associated with novel ABO alleles carrying the A2-related 1061C deletion and various missense substitutions.
BACKGROUND
The 1061delC single-nucleotide polymorphism (SNP) has been reported mostly in the context of the common A(2)[A201] allele and typically produces an A(2) phenotype. This study evaluated new A(weak) alleles, each containing 1061delC.


METHODS
Twenty samples were referred to our laboratory for analysis due to suspected A(weak) phenotypes originally detected at the referring centers. ABO Exons 1 through 7 and flanking intronic regions were sequenced. A antigen expression on red blood cells was analyzed by flow cytometry. Plasma enzyme activity was studied in one case. Molecular three-dimensional modeling techniques studied the potential effects of amino acid changes on the resulting glycosyltransferases (GTs).


RESULTS
Thirteen alleles were discovered, each featuring 1061delC with at least 1 of 12 additional SNPs in the coding region. One of these SNPs disrupts the translation initiation codon. Another constitutes the first reported change in the DVD motif. One SNP found in three alleles causes a substitution of one of the four amino acids that differentiates the wild-type A and B enzymes but plasma enzyme analysis by two methods showed only slightly decreased or normal A(2) activity. Flow cytometric analysis semiquantified the A antigen levels in 16 cases featuring 10 of the alleles and ranged from very weak to nearly A(2) levels. However, the majority of the samples displayed A(x)-like patterns. Molecular modeling of some of the GT variants indicated conformational changes that may explain the diminished A expression observed.


CONCLUSIONS
Missense SNPs were identified in 13 novel A(2)-like alleles, which produced a variety of A subgroup phenotypes.
Hult
Annika K
AK
Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Yazer
Mark H
MH
Jørgensen
René
R
Hellberg
Asa
A
Hustinx
Hein
H
Peyrard
Thierry
T
Palcic
Monica M
MM
Olsson
Martin L
ML
D000017:ABO Blood-Group System / Q000737:chemistry / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D000017:ABO Blood-Group System