7个纤维蛋白原γ链Arg275位点突变导致的遗传性异常纤维蛋白原血症家系的基因型与临床特征分析

Analysis of genotype and clinical features in 7 families with inherited dysfibrinogenemia caused by Arg275 mutations in fibrinogen γ chain

目的探讨7个纤维蛋白原(Fg)γ链275位点突变导致的遗传性异常纤维蛋白原血症家系的基因型与临床特征的关系。方法根据先证者常规凝血功能实验、Fg活性(Fg:C)及Fg抗原(Fg:Ag)等指标诊断遗传性异常纤维蛋白原血症;PCR法扩增Fg基因的全部外显子及侧翼序列,扩增产物经纯化后直接测序,明确突变位点进一步分析基因型与临床特征的关系。结果 7个家系15例患者存在Fgγ链275位点突变。其中4个家系为Arg275Cys突变,其余为Arg275His突变。15例患者有7例无症状,8例有出血相关症状:包括牙龈出血、损伤后出血难止、月经量过多等。同一突变类型(Arg275Cys或Arg275His)的家系成员间,其临床表现从无症状到重型不等。结论γ链Arg275是本地区的突变热点,其临床表型以无症状或出血表现为主,未见血栓表现。纤维蛋白原基因突变的类型与临床表型无绝对相关性。

Objective To analyse the correlation between genotype and clinical features in 7 families with inherited dysfibrinogenemia caused by Arg275 mutations in fibrinogen γ chain.Methods Diagnosis of inherited dysfibrinogenemia was confirmed by the routine coagulation tests,the activity of Fg（Fg：C） and the antigen of Fg（Fg：Ag）.All the exons and flanking sequences of Fg gene were amplified by PCR and analyzed by direct sequencing,and the relationship between the genotype and clinical characteristics was further analyzed after confirming mutation sites.Results 7 families including 15 members were diagnosed of dysfibrinogenemia caused by the mutation in Arg275.4 families carry Arg275 Cys mutation,and the rest carried Arg275 His mutation.Among them,7 people were asymptomatic,and 8 people had complained bleeding symptoms including gum bleeding,incontrollable bleeding after injury,excessive menstruation,etc.Different clinical manifestations were found among individuals with the same mutation such as Arg275 Cys or Arg275 His.Conclusion Arg275 in γ chain is the hotspot mutation in our area.Patients with Arg275 mutations in this area show asymptomatic or bleeding symptoms,while no one has thrombosis.There is no correlation between mutation types and clinical manifestations.