B糖基转移酶p.R168W突变导致B_(el)亚型的分子机制研究

Molecularmechanism of B_(el) subtype caused by mutation p. R168W of glycosyltransferase B

目的对B糖基转移酶R168W突变导致B_(el)亚型的分子机制进行研究。方法免疫血清学、ABO基因型SSP-PCR检测及直接测序患者及其家系成员ABO基因第6、第7外显子测序。构建3D分子模型,并就GTB蛋白突变对结构影响进行预测。结果经吸收放散试验在患者红细胞上检出弱B抗原,血清中未检测到抗-A、检出抗-B;患者女儿血清学结果呈正常B型。SSP-PCR结果证实患者及其女儿ABO血型基因型为O1/B和B/B型。对ABO基因第6、第7外显子测序,患者及其女儿带有c.502C>T突变,即B_(el)03等位基因,导致氨基酸置换R168W。分子模建与分析提示突变可能降低了蛋白结构的稳定性,影响了B转移酶的总体活性。结论 ABO基因c.502C>T突变通过减低GTB的稳定性导致患者出现B_(el)表型。

Objective To study the molecular mechanism of Bel subtype caused by mutation p. R168W of glycosyltrans- ferase B. Methods Serological test, SSP-PCR and direct sequence the Exon6 and Exon 7 of the ABO gene. Construct a 3D molecular model and predict the structural impact of GTB protein mutations. Results A antigen or B antigen can＇t be detected on the surface of the propositus＇ RBC, and only anti-A antibodies were detected in her serum. But serological test indicated her daughter＇s blood type was a normal B type. SSP-PCR test indicated propositus＇ ABO gene type is O1B. By gene sequencing the Exon 6 and Exon 7 of the ABO gene, a ABO Bol allel（ c. 502C〉T,p. R168W） was discoverd in both the propositus and her daughter. Through the propositus＇ daughter coexisted Bd gene with normal B gene, her blood type was a normal B type.Conclusions ABO gene c. 502C〉T mutations cause Bel phenotypes in patients by reducing the stability of GTB.