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目的:研究1例ABO血型A亚型B先证者的分子遗传学背景，探讨氨基酸变异影响糖基转移酶(GT)活性的分子机制。方法:选取2020年7月2日于郑州大学第一附属医院就诊的1例先证者作为研究对象。采用卡式法和试管法对先证者及其家系成员进行ABO血型的血清学鉴定。采用PCR-序列特异性引物扩增(PCR-SSP)及 ABO基因扩增技术对先证者的 ABO基因进行血型分子生物学鉴定。构建3D分子同源模型，对α-(1→3)-D-N-乙酰半乳糖胺基转移酶(GTA)的稳定性进行预测。 结果:先证者及其部分亲属(母亲和2个弟弟)红细胞与抗-A呈现弱凝集，与抗-B呈现强凝集，血清与Ac凝集达1～2＋，与Bc不凝集，血清学定为AwB亚型，家系分析提示其异常基因遗传自母亲。PCR-SSP检测结果显示先证者为A223B型， ABO基因测序分析显示其存在c.297A>G、c.467C>T、c.526C>G、c.657C>T、c.703G>A、c.796C>A、c.803G>C、c.930G>A杂合变异和c.1055insA插入变异，推测其基因型为 ABO* A223/ ABO* B.01，与 ABO* A1.01相比存在c.467C>T和c.1055insA变异，与 ABO* A1.02相比存在c.1055insA变异。同源建模结果显示A223型GT的C末端明显延长，且局部氨基酸及氢键网络均有改变。 结论:上述研究结果揭示了A223B亚型的分子遗传学机制，先证者存在的c.1055insA变异可能影响了GT的酶活性，最终导致A抗原减弱。

Objective:To study the molecular basis for a proband with A subtype B of the ABO blood group and explore the influence of amino acid variant on the activity of glycosyltransferase (GT).Methods:A proband who had presented at the First Affiliated Hospital of Zhengzhou University on July 2, 2020 was selected as the study subject. Serological identification of the ABO blood groups of the proband and her family members were performed by gel card and test tube methods. The ABO gene of the proband was identified by PCR-sequence specific primers (PCR-SSP) and DNA sequencing. A 3D molecular homologous model was constructed to predict the impact of the variant on the stability of α-(1→3)-D-N-acetylgalactosamine transferase (GTA). Results:The red blood cells of the proband, her mother and two younger brothers showed weak agglutination with anti-A and strong agglutination with anti-B. The sera showed 1~2+ agglutination with Ac and no agglutination with Bc. Based on the serological characteristics, the proband was identified as AwB subtype. Pedigree analysis suggested that the variant was inherited from her mother. The blood group of the proband was identified as A223B type by PCR-SSP. ABO gene sequencing analysis showed that the proband has harbored heterozygous variants of c. 297A>G, c. 467C>T, c. 526C>G, c. 657C>T, c. 703G>A, c. 796C>A, c. 803G>C, c. 930G>A and c. 1055insA. Based on the results of clone sequencing, it was speculated that the genotype was ABO* A223/ ABO* B.01. There were c. 467C>T and c. 1055insA variants compared with ABO* A1.01, and c. 1055insA variant compared with ABO* A1.02. Homologous modeling showed that the C-terminal of A223 GT was significantly prolonged, and the local amino acids and hydrogen bond network have changed. Conclusion:Above results revealed the molecular genetics mechanism of A223B subtype. The c. 1055insA variant carried by the proband may affect the enzymatic activity of GTA and ultimately lead to weakening of A antigen.