诊断学理论与实践

诊断学理论与实践 >

2024 , Vol. 23 >Issue 04: 392 - 397

DOI: https://doi.org/10.16150/j.1671-2870.2024.04.007

论著

ABO血型基因第7外显子695 T>C突变导致Bw11亚型的研究

  • 周丽华 ,
  • 沈茹 ,
  • 屈柯暄 ,
  • 王爱华 ,
  • 陈有会 ,
  • 袁志敏
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  • 1.昆明市妇幼保健院检验科，云南 昆明 650031
    2.昆明市儿童医院输血科，云南 昆明 650228
    3.陕西省肿瘤医院检验科，陕西 西安 710061
袁志敏 E-mail: yuan88328@163.com

收稿日期: 2024-03-19

  录用日期: 2024-06-20

  网络出版日期: 2024-08-25

基金资助

昆明市级基金项目(2022-11-01-020);昆明市级基金项目(2023-SW带头-20)

收起

Study on the Bw11 subtype caused by the 695 T>C mutation in exon 7 of the ABO blood group gene

  • ZHOU Lihua ,
  • SHEN Ru ,
  • QU Kexuan ,
  • WANG Aihua ,
  • CHEN Youhui ,
  • YUAN Zhimin
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  • 1. Department of Laboratory Medicine, Kunming Maternity and Child Health Care Hospital, Yunnan Kunming 650021, China
    2. Department of Blood Transfusion, Kunming Children's Hospital, Yunnan Kunming 650228, China
    3. Department of Clinical Laboratory, Shaanxi Provincial Cancer Hospital, Shaanxi Xi'an 710061, China

Received date: 2024-03-19

  Accepted date: 2024-06-20

  Online published: 2024-08-25

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摘要

目的：在中国彝族人群中发现罕见的ABO*BW.11/ABO*O.01.02血型基因亚型，探讨ABO*BW.11/ABO*O.01.02血型血清学特点、分子机制及遗传背景。方法：先证者为孕产妇，25岁，入院常规检测显示其ABO正反定型不符，在常规ABO血型血清学无法准确鉴定的情况下，对ABO基因第1-7外显子采用Sanger法进行测序分析，并利用野生型B糖基转移酶氨基酸系列同源建模，预测该位点突变对B糖基转移酶结构和功能的影响。结果：先证者及家系成员血型血清学结果与常见B亚型均不相符；ABO基因测序结果显示，先证者及家系成员4代共7人均存在ABO血型基因第7外显子存在c.695T>C错义突变，导致B糖基转移酶第232位亮氨酸被脯氨酸替换。同源建模显示，突变影响了蛋白质的肽键和氢键，导致其结构和功能发生改变，B糖基转移酶的活性降低，导致B抗原表达减弱。结论：ABO等位基因出现第7外显子c.695T>C.P.leu 232 Pro点突变是形成ABO*BW.11/ABO*O.01.02亚型的分子基础，此突变在此家系多成员中稳定遗传。

关键词： ABO亚型; 基因突变; Bw亚型; B糖基转移酶

本文引用格式

周丽华 , 沈茹 , 屈柯暄 , 王爱华 , 陈有会 , 袁志敏 . ABO血型基因第7外显子695 T>C突变导致Bw11亚型的研究[J]. 诊断学理论与实践, 2024 , 23(04) : 392 -397 . DOI: 10.16150/j.1671-2870.2024.04.007

Abstract

Objective To identify the rare ABO*BW.11/ABO*O.01.02 subtype in the Yi ethnic group in China, and to investigate the blood group serological characteristics, molecular mechanisms, and genetic background of the ABO*BW.11/ABO*O.01.02 subtype. Methods The proband was a 25-year-old pregnant woman, with ABO typing discre-pancy in routine tests on admission. Due to the inability to accurately identify the conventional ABO blood serology, exons 1-7 of the ABO gene were analyzed by sequencing using the Sanger method, and the effect of the mutation at this site on the structure and function of B glycosyltransferase was predicted using the amino acid series homology modelling of wild-type B glycosyltransferase. Results The blood group serological results of the proband and lineage were inconsistent with the typical B subtype. ABO gene sequencing unveiled a c.695T>C missense mutation in exon 7 of the ABO blood group gene in the 7 probands and family members in 4 generations, leading to the substitution of leucine by proline at position 232 of the B glycosyltransferase. Homology modeling showed that the mutation influenced the peptide and hydrogen bonds of the protein, which probably led to structural and functional alterations, diminished B-glycosyltransferase activity, and weakened expression of the B antigen. Conclusions This proband carries a point mutation in the ABO allele in exon 7 c.695T>C.P.leu 232 Pro to form the ABO*BW.11/ABO*O.01.02 subtype, and is stably inherited in multiple members of this family.

Key words： ABO subtype; gene mutation; Bw isoform; B glycosyltransferase

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