A novel cisAB allele with a missense variant (c.971T>C) in the ABO gene of a Brazilian family.

IF 1.8 4区医学 Q3 HEMATOLOGY Vox Sanguinis Pub Date : 2024-08-20 DOI:10.1111/vox.13727

Marcos Paulo Miola, Caroline Luise Prochaska, Guilherme Cardoso, Octávio Ricci Junior, Luiz Carlos de Mattos

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Abstract

Background and objectives: Missense variants in exon 7 of the ABO gene can lead to the formation of cisAB alleles. These alleles encode glycosyltransferases (GTs) capable of synthesizing both A and B antigens. In this study, we report the discovery of a novel cisAB allele and characterize it at molecular, protein and serological levels.

Materials and methods: Blood and DNA samples from the proband and seven relatives were examined using standard and modified ABO phenotyping, polymerase chain reaction-restriction fragment length polymorphism and ABO gene sequencing. We assessed the impact of the p.Leu324Ser variant on the protein structure of the mutant GT using bioinformatics tools.

Results: Molecular tests revealed a c.971T>C (p.Leu324Ser) variant in the ABO gene in five of the eight individuals. This variant results in a GT that produces more A antigens and fewer B antigens. Bioinformatics analysis suggests that the amino acid substitution (p.Leu324Ser) could potentially affect enzymatic activity and specificity of the GT.

Conclusion: We identified a novel cisAB allele resulting from a c.971T>C variant in the ABO gene. This variant led to the expression of an AB_weak phenotype.

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一个巴西家庭的 ABO 基因中出现了一个带有错义变异（c.971T>C）的新型 cisAB 等位基因。

背景和目的：ABO 基因第 7 号外显子中的错义变异可导致形成顺式AB 等位基因。这些等位基因编码的糖基转移酶（GTs）能够同时合成 A 和 B 抗原。在本研究中，我们报告发现了一种新型 cisAB 等位基因，并从分子、蛋白质和血清学水平对其进行了鉴定：使用标准和改良的 ABO 表型分析、聚合酶链式反应-限制性片段长度多态性和 ABO 基因测序法检测了原告和七名亲属的血液和 DNA 样本。我们使用生物信息学工具评估了 p.Leu324Ser 变异对突变 GT 蛋白结构的影响：结果：分子检测结果显示，8 人中有 5 人的 ABO 基因存在 c.971T>C（p.Leu324Ser）变异。该变异导致 GT 产生较多的 A 抗原和较少的 B 抗原。生物信息学分析表明，氨基酸置换（p.Leu324Ser）可能会影响 GT 的酶活性和特异性：我们发现了一个由 ABO 基因中 c.971T>C 变异产生的新型 cisAB 等位基因。该变异导致了 AB 弱表型的表达。

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来源期刊

Vox Sanguinis 医学-血液学

CiteScore

4.40

自引率

11.10%

发文量

156

审稿时长

6-12 weeks

期刊介绍： Vox Sanguinis reports on important, novel developments in transfusion medicine. Original papers, reviews and international fora are published on all aspects of blood transfusion and tissue transplantation, comprising five main sections: 1) Transfusion - Transmitted Disease and its Prevention: Identification and epidemiology of infectious agents transmissible by blood; Bacterial contamination of blood components; Donor recruitment and selection methods; Pathogen inactivation. 2) Blood Component Collection and Production: Blood collection methods and devices (including apheresis); Plasma fractionation techniques and plasma derivatives; Preparation of labile blood components; Inventory management; Hematopoietic progenitor cell collection and storage; Collection and storage of tissues; Quality management and good manufacturing practice; Automation and information technology. 3) Transfusion Medicine and New Therapies: Transfusion thresholds and audits; Haemovigilance; Clinical trials regarding appropriate haemotherapy; Non-infectious adverse affects of transfusion; Therapeutic apheresis; Support of transplant patients; Gene therapy and immunotherapy. 4) Immunohaematology and Immunogenetics: Autoimmunity in haematology; Alloimmunity of blood; Pre-transfusion testing; Immunodiagnostics; Immunobiology; Complement in immunohaematology; Blood typing reagents; Genetic markers of blood cells and serum proteins: polymorphisms and function; Genetic markers and disease; Parentage testing and forensic immunohaematology. 5) Cellular Therapy: Cell-based therapies; Stem cell sources; Stem cell processing and storage; Stem cell products; Stem cell plasticity; Regenerative medicine with cells; Cellular immunotherapy; Molecular therapy; Gene therapy.