[Molecular biological identification of a case with A223B subtype].

Q4 Medicine

中华医学遗传学杂志 Pub Date : 2024-08-10 DOI:10.3760/cma.j.cn511374-20230618-00369

Li Wang, Qiankun Yang, Shuya Wang, Ying Xie, Xue Liu, Yanli Chang, Yongkui Kong

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引用次数: 0

Abstract

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.

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[一个 A223B 亚型病例的分子生物学鉴定]。

目的研究ABO血型A亚型B的分子基础，探讨氨基酸变异对糖基转移酶（GT）活性的影响：方法：选取2020年7月2日在郑州大学第一附属医院就诊的一名ABO血型B亚型患者作为研究对象。采用凝胶卡法和试管法对该患者及其家庭成员的 ABO 血型进行血清学鉴定。通过 PCR 序列特异性引物（PCR-SSP）和 DNA 测序鉴定了该患者的 ABO 基因。构建了一个三维分子同源模型，以预测该变异对α-(1→3)-D-N-乙酰半乳糖胺转移酶（GTA）稳定性的影响：结果：疑似患者及其母亲和两个弟弟的红细胞与抗-A呈弱凝集，与抗-B呈强凝集。血清中与 Ac 呈 1~2+ 凝集，与 Bc 无凝集。根据血清学特征，该患者被确定为 AwB 亚型。血统分析表明，该变异型遗传自其母亲。通过 PCR-SSP 鉴定，该患者的血型为 A223B 型。ABO 基因测序分析表明，该患者携带 c.297A>G、c.467C>T、c.526C>G、c.657C>T、c.703G>A、c.796C>A、c.803G>C、c.930G>A 和 c.1055insA 杂合子变异。根据克隆测序结果，推测基因型为 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。同源建模显示，A223 GT的C端明显延长，局部氨基酸和氢键网络发生了变化：以上结果揭示了 A223B 亚型的分子遗传学机制。结论：上述结果揭示了 A223B 亚型的分子遗传学机制，该患者携带的 c.1055insA 变异可能会影响 GTA 的酶活性，最终导致 A 抗原的弱化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

中华医学遗传学杂志 Medicine-Medicine (all)

CiteScore

0.50

自引率

0.00%

发文量

9521

期刊介绍： Chinese Journal of Medical Genetics is a medical journal, founded in 1984, under the supervision of the China Association for Science and Technology, sponsored by the Chinese Medical Association (hosted by Sichuan University), and is now a monthly magazine, which attaches importance to academic orientation, adheres to the scientific, scholarly, advanced, and innovative, and has a certain degree of influence in the industry. Chinese Journal of Medical Genetics is a journal of Peking University, and is now included in Peking University Journal (Chinese Journal of Humanities and Social Sciences), CSCD Source Journals of Chinese Science Citation Database (with extended version), Statistical Source Journals (China Science and Technology Dissertation Outstanding Journals), Zhi.com (in Chinese), Wipu (in Chinese), Wanfang (in Chinese), CA Chemical Abstracts (U.S.), JST (Japan Science and Technology Science and Technology), and JST (Japan Science and Technology Science and Technology Research Center). ), JST (Japan Science and Technology Agency), Pж (AJ) Abstracts Journal (Russia), Copernicus Index (Poland), Cambridge Scientific Abstracts, Abstracts and Citation Database, Abstracts Magazine, Medical Abstracts, and so on.