cisAB09亚型一个家系的ABO血型血清学特征及分子遗传学分析  

Serological characteristics of ABO blood group and molecular genetic analysis of a Chinese pedigree with cisAB09 subtype

作　　者：王渊元 杨芳年[1] 沈雨青[2] 郭玉嵩[1] 姜波 杨晓俊 Wang Yuanyuan;Yang Fangnian;Shen Yuqing;Guo Yusong;Jiang Bo;Yang Xiaojun(Department of Transfusion,Zhongshan Hospital,Xiamen University,Xiamen,Fujian 361003,China;Department of Transfusion,Women and Children′s Hospital,Xiamen University,Xiamen,Fujian 361003,China;Department of Pediatric,Zhongshan Hospital,Xiamen University,Xiamen,Fujian 361003,China;Department of Transfusion,Fujian Provincial Hospital,Shengli Clinical Medical College of Fujian Medical University,Fuzhou,Fujian 350001,China)

机构地区：[1]厦门大学附属中山医院输血科,厦门361003 [2]厦门大学附属妇女儿童医院输血科,厦门361003 [3]厦门大学附属中山医院儿科,厦门361003 [4]福建医科大学省立临床医学院,福建省立医院输血科,福州350001

出　　处：《中华医学遗传学杂志》2023年第6期750-755,共6页Chinese Journal of Medical Genetics

基　　金：福建省卫生健康中青年骨干人才培养项目(2019-ZQN-32);福建医科大学启航基金项目(2018QH1119)。

摘　　要：目的探讨1个cisAB09亚型家系的ABO血型血清学特征与分子遗传学机制。方法选取2022年2月2日于厦门大学附属中山医院输血科进行ABO血型鉴定的1个cisAB09亚型家系为研究对象。采用常规ABO血型血清学检测方法对先证者及其家系成员ABO血型进行鉴定,采用血浆A和B糖基转移酶活性测定方法测定先证者及其母亲血浆中A和B糖基转移酶活性强度,采用流式细胞术检测先证者红细胞表面A、B抗原表达情况。抽取先证者及其家系成员外周静脉血样,提取基因组DNA后,对ABO基因第1~7外显子及其侧翼内含子进行测序,并对先证者及其母亲和大女儿ABO基因第7外显子进行Sanger测序验证。结果常规ABO血型血清学检测结果提示,先证者及其母亲和大女儿ABO血型初步判断为A2B表型,先证者妻子及其小女儿为O型。血浆A和B糖基转移酶活性测定结果提示,先证者及其母亲B糖基转移酶活性滴度分别为32、256,分别较A1B表型阳性对照活性滴度(128)低与高。流式细胞术检测结果显示,先证者红细胞表面A抗原表达数量减少,B抗原表达数量未见异常。ABO基因测序结果显示,先证者及其母亲和大女儿在ABO*B.01等位基因基础上,第7外显子发生c.796A>G变异,导致B糖基转移酶第266位氨基酸由甲硫氨酸变为缬氨酸,符合ABO*cisAB.09等位基因的特征。先证者及其大女儿ABO基因型为ABO*cisAB.09/ABO*O.01.01,先证者母亲为ABO*cisAB.09/ABO*B.01,先证者妻子及其小女儿为ABO*O.01.01/ABO*O.01.01。结论ABO*B.01等位基因c.796A>G变异导致B糖基转移酶第266位甲硫氨酸变为缬氨酸,是产生cisAB09亚型的分子遗传学基础,ABO*cisAB.09等位基因编码的糖基转移酶,可在红细胞表面合成正常水平B抗原和较低水平A抗原。Objective To explore the serological characteristics of ABO blood group and molecular genetic mechanism for a Chinese pedigree with cisAB09 subtype.Methods A pedigree undergoing ABO blood group examination at the Department of Transfusion,Zhongshan Hospital Affiliated to Xiamen University on February 2,2022 was selected as the study subjects.Serological assay was carried out to determine the ABO blood group of the proband and his family members.Activities of A and B glycosyltransferases in the plasma of the proband and his mother were measured with an enzymatic assay.Expression of A and B antigens on the red blood cells of the proband was analyzed by flow cytometry.Peripheral blood samples of the proband and his family members were collected.Following extraction of genomic DNA,exons 1 to 7 of the ABO gene and their flanking introns were sequenced,and Sanger sequencing of exon 7 was carried out for the proband,his elder daughter and mother.Results The results of serological assay suggested that the proband and his elder daughter and mother had an A2B phenotype,whilst his wife and younger daughter had an O phenotype.Measurement of plasma A and B glycosyltransferase activity suggested that the titers of B-glycosyltransferase activity were 32 and 256 for the proband and his mother,which were respectively below and above that of A1B phenotype-positive controls(128).Flow cytometry analysis showed that the expression of A antigen on the red blood cell surface of the proband has decreased,whilst the expression of B antigen was normal.Genetic sequencing confirmed that,in addition to an ABO*B.01 allele,the proband,his elder daughter and mother have harbored a c.796A>G variant in exon 7,which has resulted in substitution of the methionine at 266th position of the B-glycosyltransferase by valine and conformed to the characteristics of ABO*cisAB.09 allele.The genotypes of the proband and his elder daughter were determined as ABO*cisAB.09/ABO*O.01.01,his mother was ABO*cisAB.09/ABO*B.01,and his wife and younger daughter were A

关 键 词：ABO血型系统 CisAB亚型 糖基转移酶 流式细胞术 等位基因 

分 类 号：R440[医药卫生—诊断学]