摘要
目的:对1例先天性异常纤维蛋白原血症患者进行家系调查,并分析其出血与血栓风险及输血策略。方法:全自动血凝仪检测先证者及家系成员的凝血酶原时间(PT)、活化部分凝血活酶时间、凝血酶时间,纤维蛋白原活性和抗原分别用Clauss法和PT演算法进行检测。对先证者及家系成员进行血栓弹力图分析。采集先证者及其家系成员外周血标本,用PCR法扩增纤维蛋白原基因FGA、FGB和FGG的所有外显子及其侧翼序列并测序,寻找基因突变。结果:先证者的PT、活化部分凝血活酶时间正常,凝血酶时间轻度延长,纤维蛋白原活性水平降低(Clauss法);先证者姑姑、儿子和女儿的纤维蛋白原均存在不同程度降低;血栓弹力图结果提示,先证者及其家系成员(先证者儿子除外)的纤维蛋白原功能基本正常;基因分析结果发现,先证者及其子女、姑姑FGA基因2号外显子均存在6233位G/A(p.AαArg35His)杂合突变,此外家系中还发现2个多态性位点,分别是FGA基因g.9308A/G(p.AαThr331Ala)多态性和FGB基因g.12628G/A(p.BβArg478Iys)多态性;患者产前2 h输注10单位冷沉淀预防出血,生产过程及产后无明显出血。结论:FGA基因6233位G/A(p.AαArg35His)杂合突变是该先天性异常纤维蛋白原血症家系致病的生物遗传学基础。
Objective:To investigate a family with congenital dysfibrinogenemia,and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.Methods:Prothrombin time(PT),activated partial thromboplastin time(APTT)and thrombin time(TT)of the proband and her family members were detected by automatic coagulometer,fibrinogen(Fg)activity and antigen were detected by Clauss method and PT algorithm respectively.Meanwhile,thromboelastometry was analyzed for proband and her family members.Then,peripheral blood samples of the proband and her family members were collected,and all exons of FGA,FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.Results:The proband had normal APTT and PT,slightly prolonged TT,reduced level of Fg activity(Clauss method).The Fg of the proband's aunt,son and daughter all decreased to varying degrees.The results of thromboelastogram indicated that Fg function of the proband and her family members(except her son)was basically normal.Gene analysis showed that there were 6233 G/A(p.AαArg35His)heterozygous mutations in exon 2 of FGA gene in the proband,her children and aunt.In addition,2 polymorphic loci were found in the family,they were FGA gene g.9308A/G(p.AαThr331Ala)and FGB gene g.12628G/A(p.BβArg478Iys)polymorphism,respectively.The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding,and no obvious bleeding occurred during and after delivery.Conclusion:Heterozygous mutation of 6233G/A(p.AαArg35His)of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
作者
廖湘成
张珊珊
阳子骥
朱春丽
黄惠妮
罗瑞献
李思娜
谢慧琼
黎海澜
莫柱宁
LIAO Xiang-Cheng;ZHANG Shan-Shan;YANG Zi-Ji;ZHU Chun-Li;HUANG Hui-Ni;LUO Rui-Xian;LI Si-Na;XIE Hui-Qiong;LI Hai-Lan;MO Zhu-Ning(Department of Blood Transfusion,The People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,Guangxi Zhuang Autonomous Region,China;Department of Obstetrics,The People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,Guangxi Zhuang Autonomous Region,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2023年第5期1469-1474,共6页
Journal of Experimental Hematology
基金
广西自然科学基金(2021JJB140115)
广西壮族自治区卫生和计划生育委员会自筹课题(Z20180732)
广西壮族自治区卫生和计划生育委员会自筹课题(Z2015343)。