罕见Ael亚型2例的遗传学分析  

Genetic analysis of two patients with a rare Ael subtype

作　　者：贺冰冰 朱碎永[1] 黄开照 林甲进[1] He Bingbing;Zhu Suiyong;Huang Kaizhao;Lin Jiajin(The Second Affiliated Hospital,Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325027,China)

机构地区：[1]温州医科大学附属第二医院·育英儿童医院,温州325027

出　　处：《中华医学遗传学杂志》2024年第4期399-403,共5页Chinese Journal of Medical Genetics

基　　金：温州市基础性科研计划(Y20210104)。

摘　　要：目的分析2例罕见血清学放散型Ael亚型的基因测序结果。方法选取2019年6月和2020年9月分别因"子宫腺肌瘤"和"胃炎"就诊的2例女性患者作为研究对象。采用常规盐水试管凝集法和吸收放散试验鉴定Ael亚型,用Sanger法对ABO基因进行测序,用PyMOL软件构建蛋白预测结构模型,预测变异对于α-1,3-N-乙酰半乳糖氨基转移酶(GTA)结构稳定性的影响。结果2例患者血清学检测均为Ael亚型。例1测序结果为ABO*O.01.02/ABO*O.01.02,即存在p.Thr88Profs*31变异。例2测序结果为ABO*Ael.06/ABO*O.01.02,发现第7外显子存在c.425C>T(p.Met142Thr)、c.467C>T(p.Pro156Leu)变异,蛋白预测模型提示p.Met142Thr替换可能影响GTA蛋白与水分子的结合,同时改变GTA局部的氢键网络,导致酶活性下降,p.Pro156Leu替换对GTA的结构稳定性无明显影响。结论Ael亚型分子结构可能存在多样性的特点。例1基因型为261G缺失的O02/O02,例2基因型为Ael 06/O02。Objective To analyze the genetic sequences of two patients with a rare Ael blood subgroup.Methods Two female patients undergoing treatment respectively for adenomyoma of the uterus and gastritis at the Second Affiliated Hospital,Yuying Children′s Hospital of Wenzhou Medical University in June 2019 and September 2020 were selected as the study subjects.Their Ael subtypes were identified with a saline tube agglutination assay and absorption-emission assay.Sequence of the ABO gene Ael subtypes was determined by the Sanger method.The impact of genetic variants on the structural stability of N-acetylgalactosaminyl transferase(GTA)was analyzed with PyMOL software by constructing a structure predicted model.Results Both patients were determined as Ael blood subgroup.Sequencing result of patient 1 was ABO*O.01.02/ABO*O.01.02,which has resulted in a p.Thr88Profs*31 amino acid substitution.The sequencing result of patient 2 was ABO*Ael.06/ABO*O.01.02,in which c.425C>T and c.467C>T variants in exon 7 have led to p.Met142Thr and p.Pro156Leu substitutions.Prediction of the protein model speculated that the p.Met142Thr not only can change the binding of GTA protein with water molecules,but also the local hydrogen bond network of GTA,which may lead to decreased enzymatic activity.By contrast,the p.Pro156Leu variant has trivial effect on the structural stability of GTA.Conclusion The molecular structure of Ael subtypes can be diverse.The genotypes of the two patients have been respectively determined as ABO*O.01.02/ABO*O.01.02 with a G261 deletion and ABO*Ael.06/ABO*O.01.02.

关 键 词：ABO血型 Ael亚型 基因测序 蛋白结构 

分 类 号：R457.11[医药卫生—治疗学]