• Hang Lei, Jiaming Li, Can Lou, Hui Zhang, Yuqing Shen, Naizhu Su, Xuefeng Wang, Xiaohong Cai, and Yeling Lu.
• Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Blood Transfusion Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
• J Formos Med Assoc. 2024 Sep 9.

BackgroundMutations of ABO gene may cause the dysfunction of ABO glycosyltransferase (GT) that can result in weak ABO phenotypes. Here, we identified two novel weak ABO subgroup alleles and explored the mechanism that caused Ax phenotype.Materials And MethodsThe ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the mutations was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined.ResultsThe results of serological showed the subject RJ23 and RJ52 both were Ax phenotypes. The novel A alleles, Avar-1 and Avar-2 were identified according to the gene analysis. Both Avar-1 and Avar-2 harbored recombinant heterozygous alleles, specifically A2.05 and O.01.02. These alleles showcased substitutions at positions c.106G > T, c.189C > T, c.220C > T, and c.1009A > G in their respective exons. It is worth noting that the crossing-over regions of these two alleles differed from each other. In vitro expression study showed that GTA mutant impaired H to A antigen conversion, and the mutant did not affect the production of GTA though the Western bolt. In silico analysis showed that GTA mutant may change the local conformation and the stability of GT.ConclusionsThe Avar-1 and Avar-2 alleles were identified, which could cause the Ax phenotype through changing the local conformation and reducing stability of the GTA.Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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