Identification and Characterization of a Novel B Subtype Allele in the ABO Blood Group System through Clinical Genomic Analysis-Case Report

Background: The ABO blood group system plays a critical role in transfusion medicine and transplantation, with numerous subtypes exhibiting weakened antigen expression identified. This study reports a novel B subtype allele characterized by a previously unreported c.1A>G mutation in the ABO*B.01 allele, identified through clinical genomic analysis in a patient with serological ABO discrepancy. The aim is to highlight the molecular basis of this variant and its implications for accurate ABO typing.

Case Description: Case Description: In this study, we characterized a novel B subtype allele in a 54-year-old male patient presenting with ABO blood group discrepancy at Shandong Provincial Hospital, China. Comprehensive serological analysis demonstrated weak B antigen expression (1+ reaction strength) on erythrocytes with corresponding strong anti-A activity (4+) in plasma. The patient underwent surgery without requiring blood transfusion, as no significant hemorrhage occurred intraoperatively. Molecular characterization through complete sequencing of ABO gene exons 1-7 revealed a unique mutational profile: (1) a c.1A>G variant in exon 1; (2) compound mutations in exon 6 including a c.261delG (p.Thr88Profs31) frameshift mutation and c.297A>G substitution; and (3) multiple exon 7 variants (c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C, and c.930G>A).

Conclusions: This study reports a novel B subtype allele characterized by the c.1A>G variant on an ABO*B.01 background (GenBank accession number PP920240). The c.1A>G variant affects the translation initiation codon and is the primary finding defining this new allele, while the additional variants in exons 6 and 7 are consistent with the known ABO*O.01.01 and ABO*B.01 alleles. These findings highlight the need for genetic analysis in ABO typing to ensure transfusion safety. Further studies should characterize the functional effects of this variant.