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Weak A phenotypes associated with novel ABO alleles carrying the A 2 ‐related 1061C deletion and various missense substitutions
Author(s) -
Hult Annika K.,
Yazer Mark H.,
Jørgensen René,
Hellberg Åsa,
Hustinx Hein,
Peyrard Thierry,
Palcic Monica M.,
Olsson Martin L.
Publication year - 2010
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.1537-2995.2010.02670.x
Subject(s) - missense mutation , allele , abo blood group system , genetics , single nucleotide polymorphism , biology , phenotype , snp , microbiology and biotechnology , exon , context (archaeology) , gene , genotype , paleontology
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. STUDY DESIGN AND 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. CONCLUSION: Missense SNPs were identified in 13 novel A 2 ‐like alleles, which produced a variety of A subgroup phenotypes.