A clue to the basis of allelic enhancement: occurrence of the Ax subgroup in the offspring of blood group O parents.
Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analysed by PCR-ASP/restriction fragment length polymorphism genotyping and DNA sequencing. The propositus' RBCs were very weakly agglutinated with monoclonal anti-A but distinctly with polyclonal anti-A,B, i.e. typical for Ax. Serum anti-A1 (titre 4) and -B were present. Her parents' blood groups were both clearly O, with titres of serum anti-A1, and -A at 16 and 4, respectively. Adsorption/ elution studies demonstrated A antigen on the daughter's cells only. The ABO genotypes were: mother, AxO1; father, O1vO2; and propositus, AxO2. The Ax allele was an A1-O1v hybrid allele with a crossing-over breakpoint between positions 235 and 446 in intron 6 (Ax-4). Compared to the A1 glycosyltransferase, this allele predicts a protein with two amino acid substitutions (Phe216Ile and Met277Val) known to yield either weakly expressed or no A antigen on RBCs. This study suggests that the nature of the ABO allele in trans can influence A antigen expression, a phenomenon previously described as allelic enhancement (or reinforcement). Potential mechanisms for this are discussed.
Olsson
M L
ML
Division of Haematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University & the Blood Centre, University Hospital, Lund, Sweden. martin_l.olsson@med.lu.se
Michalewska
B
B
Hellberg
A
A
Walaszczyk
A
A
Chester
M A
MA
D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D003434:Crossing Over, Genetic; D005190:Family; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D040641:Quantitative Trait Loci
D000017:ABO Blood-Group System