A novel splice- site mutation in the ABO gene causing an ABO Bel subgroup phenotype. ABO c.28+3insT

At the ABO blood group gene locus a broad genetic diversity with polymorphisms associated with phenotypic variations has been reported. Bweak subgroup alleles have been correlated with the Bx, Bel and Bm ABO subgroup phenotypes. Here we describe a novel ABO B allele, characterized by an insertion based mutation in the coding sequence of the gene identified in a patient with aberrant weak B phenotype.Serologic ABO blood group typing (Bio-Rad) and allele-specific amplification of Exon 1 to Exon 7 were carried (Peqlab Biotechnology) out. Sequencing of the ABO gene and regulatory regions was done (AB 3500, Applied Biosystems).For Bel characterization adsorption/elution studies of the patient red blood cells were performed with human anti-B serum followed by acid elution technique.ABO blood grouping using monoclonal and human antibodies showed absence of A and B antigens indicating an ABO blood group O phenotype, while adsorption-elution of the individual´s RBCs confirmed the presence of B antigen. Allele-specific sequence analysis revealed a novel ABO*B.01 - like allele with an insertion of T in Intron 1 (c.28+3insT) inherited with an inactive ABO*O1 allele in trans. The novel insertion is located at the intron-exon junction and may result in aberrant ABO mRNA transcripts. The patient´s Bel ABO subtype most likely is caused by the inherited variant B allele.