Abstract

Background - Variants of the ABO gene that can lead to the malfunctioning of ABO glycosyltransferase (GT) and consequently result in weakened ABO phenotype. In this study, we investigated the mechanism behind the emergence of the AweakB phenotype associated with this novel weak ABO subgroup allele.

Materials and methods - The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The total glycosyltransferase transfer capacity in serum was examined, and the flow cytometry was applied to detect the A antigen on the red blood cells. The role of the novel mutation was evaluated by 3D model, predicting protein structure and stability changes.

Results - The serological results revealed that the individual had an AweakB phenotype. A novel single nucleotide variant (SNV) c.300C>G (p.F100L) based on ABO*A1.02, was detected through gene analysis, confirming the genotype of the subject as AW-var/B.01. Flow cytometric analysis of the A antigen on red blood cells demonstrated a very weak expression of A antigens in the proband, and the catalytic ability analysis indicated that the GTA had almost completely lost its ability to convert O type red blood cells into A type red blood cells. In silico analysis suggested that the SNV c.300C>G on the A1.02 might potentially decrease the stability of GTA, as indicated by the ΔΔG values -1.841. However, it was noted that the hydrogen bond structure around the 100 site did not show significant changes between the wild-type and variant GTA.

Discussion - One novel AW allele was identified and the SNV c.300C>G (p. F100L) can cause the AweakB phenotype through reducing stability of the GTA.

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Authors

Yuqing Shen - Department of Transfusion, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China; Department of Transfusion, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China

Junshun Gong - Department of Transfusion, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

Yuyu Zhang - Blood Group Reference Laboratory, Shanghai Institute of Blood Transfusion, Shanghai Blood Center, Shanghai, China

Naizhu Su - Department of Transfusion, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

Lou Can - Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Jiaming Li - Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Dong Xiang - Blood Group Reference Laboratory, Shanghai Institute of Blood Transfusion, Shanghai Blood Center, Shanghai, China

Xiaohong Cai - Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Hang Lei - Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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