纤维蛋白原Aα链Gly31Glu突变导致的遗传性异常纤维蛋白原血症的家系分析  

Analysis of a pedigree affected with congenital dysfibrinogenemia due to a novel Gly31Glu mutation of FGA gene

作　　者：王晓欧[1] 杨啸 杨威[1] 舒旷怡[1] 李帆帆[1] 柳洁[1] 章赵华[1] 李姗姗[1] 江明华[1] Wang Xiaoou;Yang Xiao;Yang Wei;Shu Kuangyi;Li Fanfan;Liu Jie;Zhang Zhaohua;Li Shanshan;Jiang Minghua(Center of Laboratory Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Yuying Children's Hospital,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医学检验中心,浙江325027

出　　处：《中华医学遗传学杂志》2019年第9期901-904,共4页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金(LY13 H200003);浙江省医药卫生科技项目(2016RCA023);浙江省医药卫生科技项目(2015KYA155);温州市公益性科技计划项目(2019Y0172).

摘　　要：目的 对1例遗传性异常纤维蛋白原血症家系进行临床表型和基因型分析,以探讨其发病机制.方法 用ADVIA2400型生化分析仪检测家系所有成员的肝、肾功能;用STA-R全自动血凝仪检测其血浆凝血酶原时间、部分活化凝血活酶时间、凝血酶时间、纤维蛋白(原)降解产物、D二聚体及TT的硫酸鱼精蛋白纠正实验;分别用Clauss法和免疫散射比浊法检测血浆纤维蛋白原活性和纤维蛋白原抗原;用PCR扩增纤维蛋白原基因FGA、FGB和FGG的所有外显子及侧翼序列,测序寻找突变位点,并排除基因多态性;采用生物学信息学预测软件(PolyPhen-2、SIFT和Mutation Taster)分析突变对蛋白质功能的影响.结果 先证者及家系成员肝、肾功能均正常;先证者TT(31.8 s)明显延长且不能被硫酸鱼精蛋白校正,血浆纤维蛋白原活性明显降低(1.68 g/L)但纤维蛋白原抗原含量正常(3.78 g/L),其他凝血指标正常;其母检测结果与其相似.基因分析显示先证者及其母亲FGA基因第2外显子c.92G>A(p.Gly31Glu)存在杂合性错义变异,突变来源于母系.3个生物信息学软件预测结果均提示此突变可影响蛋白质功能.结论 纤维蛋白原 Αα链Gly31Glu突变是致先证者及其母亲异常纤维蛋白原血症的分子基础,该突变尚未见报道.Objective To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia.Methods Liver and kidney functions of the proband and her relatives were determined.Coagulation tests including prothrombin time(PT),activated partial thromboplastin time(APTT)and thrombin time(TT),fibrin(ogen)degradation products(FDPs),D-dimer(D-D)and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members.The activity and antigen of fibrinogen(Fg)in plasma were measured by Clauss method and immunonephelometry method,respectively.All of the exons and exons-intron boundaries of the three fibrinogen genes(FGA,FGB and FGG)were subjected to PCR amplification and Sanger sequencing.Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2,SIFT and Mutation Taster.Results The proband had normal PT,APTT,FDPs,D-D and prolonged TT(31.8 s).The activity of fibrinogen(Fg)in plasma was significantly decreased but the antigen was normal.Genetic analysis revealed a heterozygous c.92G>A(p.Gly31Glu)mutation in exon 2 of the FGA gene.Family studies revealed that the mother carried the same mutation.Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein.Conclusion The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.

关 键 词：异常纤维蛋白原血症 凝血酶时间 纤维蛋白原 基因突变 

分 类 号：R5[医药卫生—内科学]