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)
Study on the Bw11 subtype caused by the 695 T>C mutation in exon 7 of the ABO blood group gene
Received date: 2024-03-19
Accepted date: 2024-06-20
Online published: 2024-08-25
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。
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
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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