title: Weak A phenotypes associated with novel ABO alleles carrying the A2-related 1061C deletion and various missense substitutions.
abstract: 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.
authors.affiliation: Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Annika K
authors.initials: AK
authors.lastname: Hult
authors.forename: Mark H
authors.initials: MH
authors.lastname: Yazer
authors.forename: René
authors.initials: R
authors.lastname: Jørgensen
authors.forename: Asa
authors.initials: A
authors.lastname: Hellberg
authors.forename: Hein
authors.initials: H
authors.lastname: Hustinx
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Monica M
authors.initials: MM
authors.lastname: Palcic
authors.forename: Martin L
authors.initials: ML
authors.lastname: Olsson
mesh_terms: 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
chemical_list: D000017:ABO Blood-Group System