诊断学理论与实践

诊断学理论与实践 >

2024 , Vol. 23 >Issue 06: 619 - 623

DOI: https://doi.org/10.16150/j.1671-2870.2024.06.009

论著

ABO基因突变致A抗原弱表达分析

  • 顾玉微 ,
  • 王成云 ,
  • 顾萍 ,
  • 潘秋辉 ,
  • 王静
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  • 上海交通大学医学院附属上海儿童医学中心输血科，上海 200127
王静 E-mail：wjeney@163.com

收稿日期: 2024-01-10

  网络出版日期: 2024-08-25

基金资助

国家自然科学基金青年项目(82000183)

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Analysis of weak expression of A antigen induced by ABO gene mutation

  • GU Yuwei ,
  • WANG Chengyun ,
  • GU Ping ,
  • PAN Qiuhui ,
  • WANG Jing
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  • Department of Blood Transfusion, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

Received date: 2024-01-10

  Online published: 2024-08-25

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摘要

目的： 对ABO血清学检测抗原弱表达患者行血型基因分型，分析抗原弱表达的原因。方法： 血清学检测采用微柱凝胶法，血型基因分型采用PCR结合直接测序方法检测患者ABO基因增强子、启动子、第1至第7号外显子以及其相邻的内含子区域，选用软件PolyPhen-2对突变进行核苷酸功能预测和3D结构图绘制。结果： 血清学检测，患者红细胞与抗A抗体反应弱凝集（2+）、与抗B抗体反应凝集（4+），患者血清与A1细胞反应弱凝集（2+），与B细胞和O细胞反应不凝集，其ABO血型血清学表现型为AweakB，抗球蛋白试验和抗体筛查试验均为阴性。DNA测序提示6号外显子存在c.297 A>G突变，7号外显子存在c.526 C>G、c.657 C>T、c.703 G>A、c.796 C>A、c.803 G>C、c.930 G>A、c.940 A>G突变。查询国际输血协会数据库，c.940 A>G突变导致ABO基因编码糖基转移酶（glycosyl transferase A，GTA）发生p.Lys314Glu突变，从而导致A酶活性减弱，患者基因型为ABO*AW.37/B.01。结论： 本例患者根据ABO血型DNA测序结果发现其7号外显子存在c.940 A>G突变，此突变位点可使编码的氨基酸发生改变即p.Lys314Glu突变，从而导致A抗原弱表达。

关键词： ABO血型; 基因型; 外显子; 抗原弱表达

本文引用格式

顾玉微 , 王成云 , 顾萍 , 潘秋辉 , 王静 . ABO基因突变致A抗原弱表达分析[J]. 诊断学理论与实践, 2024 , 23(06) : 619 -623 . DOI: 10.16150/j.1671-2870.2024.06.009

Abstract

Objective This study aims to perform blood group genotyping on patients with weak antigen expression detected by ABO serology and analyze the causes of weak antigen expression. Methods Serological detection was carried out by the microcolumn gel method. Blood group genotyping was conducted by PCR combined with direct sequencing. The enhancer, promoter, exons 1-7, and adjacent intron regions of the ABO blood group gene in the patients were tested. The software PolyPhen-2 was used to predict the nucleotide function of mutations and to generate a 3D structural model. Results In one male patient, the red blood cells showed weak agglutination with anti-A antibody (2+) and agglutination with anti-B antibody (4+). The patient’s serum showed weak agglutination with A1 cells (2+), and no agglutination with B cells and O cells. The serological phenotype of the ABO blood group was AweakB, with both the direct antiglobulin test and antibody screening test being negative. The results of DNA sequencing showed that there were c.297 A>G mutation in exon 6, and c.526 C>G, c.657 C>T, c.703 G>A, c.796 C>A, c.803 G>C, c.930 G>A and c.940 A>G mutations in exon 7. According to the International Blood Transfusion Association database, the c.940 A>G mutation leads to p.Lys314Glu mutation in the ABO gene-encoded glycosyl transferase A (GTA), resulting in decreased A enzyme activity. The patient’s genotype was ABO*AW.37/B.01. Conclusions In this patient, exon 7 of the ABO blood group gene has a c.940 A>G mutation. This mutation site can change the encoded amino acid, namely p.Lys314Glu, resul-ting in weak expression of A antigen.

Key words： ABO blood group; Genotype; Exon; Weak antigen expression

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