A weak blood group A phenotype caused by a new mutation at the ABO locus

A number of alleles have been described for ABO encoding for common and rare ABO blood group phenotypes. Critical mutations in the coding sequence of ABO that may confer the different specificity and activity of the glycosyltransferases encoded by this gene locus have been identified.

Three unrelated patients from Germany, Turkey, and Bosnia who were diagnosed as having variant A subgroups were subjected to extended ABO typing. Serologic investigations were performed with standard methods. The genetic basis of the ABO phenotypes was determined by haplotype-specific sequence analysis of the last two exons (exons 6 and 7) of ABO and the intervening intron.

The RBCs of all three patients showed serologic A characteristics being similar to subgroup A(x). The serum of all three patients contained weakly reactive anti-A. In all three patients, sequence analysis indicated an A allele with a nucleotide sequence identical to ABO(*)A101 except for a single-base substitution in exon 7 at position 502, where C was replaced by G. This point mutation resulted in an amino acid exchange from arginine to glycine at position 168. The nucleotide sequence of intron 6 of the A allele was found to be identical to the ABO(*)A101 sequence in each patient.

This study suggests that a variant A phenotype can arise from the new R168G polymorphism, reflecting the importance of this region for the ABO transferase efficiency.