Department of Molecular Biology, Faculty of Medicine of São José do Rio Preto - FAMERP, São José do Rio Preto, São Paulo, Brazil.
Regional Blood Center of São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.
Vox Sang. 2024 Nov;119(11):1196-1200. doi: 10.1111/vox.13727. Epub 2024 Aug 20.
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.
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.
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.
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 phenotype.
ABO 基因外显子 7 中的错义变异可导致顺式 AB 等位基因的形成。这些等位基因编码能够合成 A 和 B 抗原的糖基转移酶（GT）。本研究旨在报告一种新的顺式 AB 等位基因的发现，并在分子、蛋白和血清学水平对其进行特征描述。
采用标准和改良的 ABO 表型、聚合酶链反应-限制性片段长度多态性和 ABO 基因测序方法，对先证者和 7 位亲属的血液和 DNA 样本进行检测。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。
分子检测显示，8 个人中有 5 个人的 ABO 基因存在 c.971T>C（p.Leu324Ser）变异。该变异导致 GT 产生更多的 A 抗原和更少的 B 抗原。生物信息学分析表明，氨基酸取代（p.Leu324Ser）可能会影响 GT 的酶活性和特异性。
我们发现了一种由 ABO 基因 c.971T>C 变异引起的新的顺式 AB 等位基因。该变异导致 AB 表型的表达。
