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目的 对1例遗传性异常纤维蛋白原(Fg)血症家系进行表型诊断和基因分析,探讨其分子发病机制.方法 采集先证者及家系(共3代6人)外周血,上层血浆在全自动血凝仪上检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原活性(Fg:C)、凝血酶时间(TT)、纤维蛋白(原)降解产物(FDP)、D-二聚体(D-D)、抗凝血酶活性(AT:A)和纤溶酶原活性(PLG∶ A);采用免疫比浊法检测纤维蛋白原抗原(Fg∶ Ag)含量.采用常规血栓弹力图(TEG)和功能性Fg TEG进行凝血功能综合评价及功能性Fg评估;利用下层血细胞提取DNA,采用PCR扩增Fg 3个基因FGA、FGB、FGG的所有外显子和侧翼序列、5’和3’非翻译区,扩增产物经纯化后直接测序分析,寻找基因突变.采用生物信息学软件(PolyPhen-2、Mutation Taster和SIFT)分析突变位点对蛋白质的影响;同时采用Clusta1X软件分析突变位点的物种保守性.结果 先证者以及小女儿Fg∶C、TT、PT明显异常,分别为0.88g/L、31.7s、16.0s和1.01g/L、26.6s、15.3s,而Fg∶ Ag均在正常参考范围,分别为3.54g/L和3.29g/L;家系其他成员凝血指标均在正常参考范围内.功能性Fg TEG结果显示先证者及其小女儿存在Fg功能缺陷.先证者以及小女儿FGA基因2号外显子发生了c.104G＞A杂合错义突变,即CGT→CAT,导致p.Arg16His杂合突变.生物信息学软件预测结果表明,该突变可影响蛋白质功能并导致相应疾病的发生.结论 该遗传性异常纤维蛋白原血症患者的FGA基因存在c.104G＞A杂合错义突变,此突变与患者的Fg∶C下降有关.“,”Objective:To analyze the phenotype and genotype of a Chinese pedigree with inherited dysfibrinogenemia and discuss the molecular mechanism of the disease.Methods:The peripheral blood was gathered of the proband and their family members (six persons of three generations),the plasm were used to detecte prothrombin time (PT) 、activedparial thromboplastin time (APTT) 、fibrinogen activity、thrombin time (TT) 、fibrin (ogen) degradation products (FDP) 、D-Dimer (D-D) 、antithrombin activity (AT:C) and plasminogen activity (PLG:A) on a STAGO automatic blood coagulation analyzer,fibrinogen antigen were analysed with an Immune turbidimetry.Conventional TEG and functional TEG Fg were performed with to evaluate the coagulation function and the level of functional Fg.The DNA were extracted from lower blood,all exons and flanking sequence,5'and 3'untranslated sections of Fg gene were amplified by using PCR,the amplification products were analysed to search for mutations after purification.Three biological information softwares (PolyPhen-2 、Mutation Taster and SIFr) were applicated to forecast the possible.effect of the mutation on the protein function;ClustalX was used to analyse the species conservatism of the mutation site.Result:The result of Fg activity、Fg antigen、TT、PT of the proband and her younger daughter was 0.88g/L、3.54 g/L、31.7s、16.0s and 1.01g/L、3.29 g/L、26.6s、15.3s,the coagulation indicators of other members were in the normal range;Functional Fg TEG results showed that the proband and her younger daughter had Fg functional defection.DNA sequencing has showed that the proband and her younger daughter had the same hybrid missense mutationof c.104 G＞A in the second exon of the FGA gene which caused a p.Arg16His change.The consequences of the softwares showed that the mutation could affect the Fg protein function that may cause disease.Conclusions:A hybrid missense mutation of c.104 G＞A in the second exon of the FGA gene has been found in the proband,which probably has the relationship with the decline of Fg activity.