α链Gly36Ser突变致异常纤维蛋白原血症家族的纤维蛋白原功能分析  

Functional analysis of abnormal fibrinogen caused by mutation in the α chain: p.Gly36Ser

作　　者：毕美霞 郑雪玲 李北 岳晓静 高润光 Bi Meixia;Zheng Xueling;Li Bei;Yue Xiaojing;Gao Runguang(Department of Laboratory Medicine Jiaozuo Hospital of Traditional Chinese Medicine,Jiaozuo 454000,China;Department of Laboratory Medicine Jiaozuo Women's and Children's Hospital,Jiaozuo 454002,China)

机构地区：[1]焦作市中医院检验科PCR实验室,焦作454000 [2]焦作市妇幼保健院PCR实验室,焦作454002

出　　处：《血栓与止血学》2023年第1期25-30,共6页Chinese Journal of Thrombosis and Hemostasis

基　　金：河南省焦作市科技局科技计划项目(202040191)。

摘　　要：目的 分析一个由α链Gly36Ser突变引起、患病成员症状有差异的遗传性异常纤维蛋白原血症家族的纤维蛋白原(fibrinogen, Fg)功能。方法 收集该遗传性异常纤维蛋白原血症家族患者外周血样本,常规凝血功能试验筛查家族成员凝血功能;NGS法筛查Fg基因(FGA、FGB、FGG)突变位点,Sanger法验证以确认突变;生物信息软件预测突变Fg功能;血栓弹力图(TEG)和功能性Fg TEG试验对家族所有患病者进行Fg凝聚功能评价;Fg动态凝聚试验和纤维蛋白溶解试验检测患病成员纤维蛋白聚集和溶解功能。结果 该家族共有突变基因携带者11名,常规凝血实验和基因突变检测均符合异常纤维蛋白原血症的诊断;11名突变基因携带者经Sanger法验证为同一突变位点;Uniprot和SWISS-MODEL等预测软件均表明该突变为影响纤维蛋白原聚合的有害突变;家族突变基因携带者中5名有症状者TEG相关参数与无症状者相比明显变化,Fg凝集试验显示该5名有症状者凝固曲线起峰时间明显延长且峰值降低;纤维蛋白溶解试验表明家系中多数(7/11)突变基因携带者纤维蛋白在限定时间中不能完全溶解。结论 α链Gly36Ser突变的异常纤维蛋白原血症患者症状可有差异,应全面分析该突变引起的异常纤维蛋白血症家系的基因型和表型,并长期观察患者纤维蛋白功能和凝血功能的变化。Objective To analyze the fibrinogen function of a dysfibrinemia family withheterogeneous symptoms caused by the Gly36Ser mutation in the α chain.Methods To collect theperipheral routine coagulation function tests was used to screen the coagulation function of the whole familymembers, NGS method was used to screen Fg gene(FGA, FGB, FGG) mutation sites, Sanger method wasused to confirm the mutation;bioinformatics software was used to predict the function of the mutant proteinand compar the experimental results and patient symptoms;thrombelastography( TEG) and functional FgTEG test were to evaluate the coagulation function of all patients in the family;fibrin dynamic aggregationtest and fibrinolysis test were used to detect the fibrin aggregation and dissolution function of diseasedmembers.Results There were 11 mutation carriers in this family, routine coagulation experiments andgenetic testing were used to confirm the diagnosis of congenital dysfibrinogenemia( CD);11 mutationcarriers ware verified as the same mutation site by Sanger method;prediction software such as Uniprot and SWISS-MODEL indicated that the mutation is a harmful mutation of fibrinogen polymerization;the TEG-related parameters of 5 symptomatic patients in the family were significantly higher than those ofasymptomatic mutation carriers. The fibrinogen coagulation test showed that the peak time of thecoagulation curve of five symptomatic patients was significantly prolonged and the peak value wasdecreased. The fibrinolysis test showed that most mutation carriers( 7/11) in the family’s fibrin could not becompletely dissolved within a limited time.Conclusion The symptoms of CD( αGly36Ser) could be variablewith the same mutation site. The genotype and phenotype analysis of this genetic disease should becomprehensive, and the impact of specific mutations on patients should be observed for a long time,especially focus on the functional change of fibrinogen.

关 键 词：遗传性异常纤维蛋白原血症 αGly36Ser突变 纤维蛋白原 血栓弹力图 

分 类 号：R554.5[医药卫生—血液循环系统疾病]