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摘要: 目的 分析Bel亚型家系的血清学特点及分子机制，并探讨其临床安全输血的策略。方法 采用经典血清学法、吸收放散法、聚合酶链反应-碱基序列直接测序法(PCR-SBT法)来鉴定家系成员的ABO血型；构建B基因编码半乳糖基转移酶(GTB)突变体空间模型，预测GTB突变体的稳定性。结果 先证者及其父亲血清学表型为Bel，其姐姐及女儿表现型为O型。基因测序显示，先证者及其父亲、姐姐、女儿携带BEL.03等位基因。三维分子模型结构显示，突变型GTB丢失了2个氢键后引入了1个新的氢键，导致突变体酶催化中心局部空间结构发生改变，采用SNPeffect软件计算突变体的自由能差值(ΔΔG)升高，表明蛋白稳定性下降。结论 Bel亚型在血型血清学试验上极易误判为O型，联合基因测序可精准判定ABO血型，从而保障临床输血安全有效。Abstract: Objective Analyze the serological characteristics and molecular mechanisms of Bel subtype families, and explore strategies for safe clinical blood transfusion.Methods The ABO blood types of family members were identified using classical serological methods, absorption and release assays, and PCR SBT genotyping; Construct a spatial model of GTB mutants to predict their stability.Results The serological phenotype of the proband and his father is Bel, while the phenotype of his sister and daughter is O. Genetic sequencing shows that the proband and their father, sister and daughter carry the BEL.03 allele. The three-dimensional molecular model structure shows that the mutant GTB lost two hydrogen bonds and introduced a new one, resulting in a change in the local spatial structure of the mutant enzyme catalytic center. The free energy difference(ΔΔG) of the mutant was calculated using SNP effect software, indicating a decrease in protein stability.Conclusion The Bel subtype is easily misdiagnosed as O type in blood type serological tests, and combined with gene sequencing, it can accurately determine ABO blood type, thereby ensuring the safety and effectiveness of clinical blood transfusion.
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Key words:
- ABO blood type /
- Bel subtype /
- gene sequencing /
- molecular model
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表 1 Bel亚型家系成员血型血清学结果
样本 正定型 反定型 吸收放散试验 血清学表型 基因型 抗-A 抗-B 抗-H A1C Bc Oc 自身对照 Bc(单克隆抗-B) Bc(人源抗-B) 1 0 0 4+ 4+ 1+s 0 0 1+ / Bel ABO*BEL.03/O.01.02 2 0 0 4+ 4+ 1+ 0 0 1+w / Bel ABO*BEL.03/O.01.02 3 0 0 4+ 4+ 4+ 0 0 / / O ABO*O.01.01/O.01.02 4 4+ 0 1+ 0 4+ 0 0 / / A ABO*A1.02/O.01.01 5 0 0 4+ 4+ 1+ 0 0 0 0 O ABO*BEL.03/O.01.01 6 0 0 4+ 4+ 1+w 0 0 0 0 O ABO*BEL.03/O.01.01 注：样本1~6分别代表先证者及其父亲、母亲、丈夫、姐姐、女儿；s：凝集强度增强；w：凝集强度减弱；/：未测。 
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表 2 先证者ABO血型单体型
单倍型1 单倍型2 表现型 等位基因 碱基替换 氨基酸替换 表现型 等位基因 碱基替换 氨基酸替换 Bel ABO*BEL.03 c.297A>G p.Arg168Trp O ABO*O.01.02 c.106G>T p.Val36Phe c.526C>G p.Arg176Gly c.188G>A p.Arg63His c.657C>T p.Gly235Ser c.189C>T p.Pro74Ser c.703G>A p.Leu266Met c.220C>T p.Thr88Profs*31 c.796C>A p.Gly268Ala c.261delG c.803G>C c.297A>G c.930G>A c.646T>A c.502C>T c.681G>A c.771C>T c.829G>A
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