一例B糖基转移酶基因缺失导致Bel变异型的分子机制  

Study of the molecular basis for an individual with Bel variant due to deletion of B glycosyltransferase gene

作　　者：应燕玲[1] 洪小珍[1] 陈舒[1] 许先国[1] 马开荣[1] 蓝小飞[1] 何吉[1] 朱发明[1] 

机构地区：[1]浙江省血液中心,卫生部血液安全研究重点实验室,浙江省血液安全研究重点实验室,杭州310052

出　　处：《中华医学遗传学杂志》2017年第3期423-426,共4页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金（LY17H080003）;浙江省公益技术项目（2013C33193）;浙江医药卫生科技项目（WKJ-ZJ-1510,2012RCB010,2016RCB006）

摘　　要：目的探讨1例ABO血型Bel变异型的分子机制。方法血清学方法检测样本的红细胞和血清；用PCR扩增其ABO基因的全部外显子及侧翼的内含子序列，并进行双向测序。通过克隆进行单体型分析，并模建分析其糖基转移酶的三维结构。结果吸收放散实验检出样本红细胞上有表达极弱的B抗原，血清学表现为Bel。直接测序分析发现ABO基因第6外显子261del／G杂合，第7外显子297A／G、484del／G、526c／G、657C／T、703G／A、796C／A、803G／C、930G／A杂合。单倍型克隆测序发现有1个O01等位基因和1个新的B等位基因。与B101参考序列相比，新的B等位基因序列中存在484delG，并被红细胞血型抗原基因突变数据库（dRBC NCBI）命名为B120。484delG可导致B糖基转移酶阅读框发生改变而提前终止，三维结构分析显示其蛋白仅保留部分N端结构区域，为不完整的转移酶蛋白。结论B转移酶基因第484位缺失G可引起酶活性缺失或显著减弱，从而导致Bel表型。Objective To explore the molecular basis of an individual with Bel variant of the ABO blood group. Methods The ABO antigen and serum antibody of the individual were detected by serological method. All coding regions and flanking introns of the ABO gene were amplified with PCR and sequenced bidirectionally. The haplotypes of the individual were analyzed by cloning and sequencing. A three dimensional model of the mutant protein was constructed and analyzed. Results The individual has expressed a very weak B antigen on its red blood cells by absorption and elution testing, which was identified as a Bel variant phenotype. The heterozygous sites in exon 6 （261del/G） and exon 7 （297A/G, 484del/G, 526C/G, 657C/T, 70aG/A, 796C/A, 803G/C, 930G/A） of the coding region of the ABO gene were identified by direct sequencing. Haplotype analysis showed that the individual has carried an O01 allele and a novel B allele. The sequence of the novel B allele was identical to B101 except for a del G at nucleotide position 484 （484delG）, which was nominated as B120 by the Blood Group Antigen Gene Mutation Database （dbRBC NCBI）. The 484delG mutation of the B allele has led to a reading frame shift and created a premature terminal codon for the glycosyltransferase （GT） enzyme. Prediction of the 3D structure suggested that the GT enzyme has become an incomplete protein only with its N-terminal region. Conclusion The 484delG mutation of the glycosyltransferase B gene has probably abolished or reduced the enzymatic activity and resulted in the Bel variant phenotype.

关 键 词：Bel变异型 ABO基因 缺失突变 

分 类 号：R440[医药卫生—诊断学] R457.11[医药卫生—临床医学]