Abstract
Background - Accurate ABO typing is essential for transfusion safety, yet weak A/B subgroups continue to present diagnostic challenges. Although most weakened ABO antigen expressions are linked to missense mutations or small indels within coding regions, the contribution of non-coding regulatory variants −especially large structural alterations− remains insufficiently characterized. Standard genotyping methods, including Sanger sequencing and targeted
next-generation sequencing, often fail to detect large upstream deletions, leaving some serological-genotypic discrepancies unresolved in donors and patients. Such gaps hinder accurate transfusion risk assessment. To clarify these mechanisms, this study performed detailed ABO blood typing in a donor with an A subgroup and his family and explored the molecular basis for weakened A antigen expression.
Materials and methods - ABO phenotypes of the proband and his parents, spouse, two daughters, and son were determined using serological testing. Full-length ABO gene sequencing was then performed using third-generation single-molecule sequencing.
Results - The proband, his father, and his son displayed the Aweak phenotype. All three carried a heterozygous 12,309-bp deletion located upstream of the ABO gene promoter, along with a normal ABOA1.02 allele. The remaining family members carried genotypes ABOO.01.01/ABOO.01.01 (mother), ABOB.01/ABOO.01.02 (wife), ABOB.01/ABOO.01.01 (daughter 1), and ABOO.01.01/ABOO.01.02 (daughter 2). No variants were detected in coding regions, introns, or splice sites. Pedigree analysis confirmed that the proband inherited the ABOA1.02 allele with the 12.3-kb deletion from his father and passed it to his son.
Discussion - This study identifies, for the first time, a large 12.3-kb upstream deletion of the ABO promoter responsible for weakened erythrocyte A antigen expression. The finding expands current understanding of regulatory mechanisms underlying weak ABO phenotypes and highlights the value of advanced sequencing for transfusion safety.
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Authors
jiancheng Liu
Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
Feng Shao Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
Jie Yang Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
Xiaoyin Mao Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
Xiaoyun Bu Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
Jing Hai Blood Group Reference Laboratory, Ningxia Blood Center, Yinchuan, China
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