Wang Xiaoou, Yang Xiao, Wang Jinle, Shu Kuangyi, Li Fanfan, Yang Wei, Ruan Jichen, Wang Shishi, Jiang Minghua
Centre of Laboratory Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Zhejiang 325027, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Dec 10;37(12):1391-1394. doi: 10.3760/cma.j.cn511374-20191120-00595.
To explore the genetic basis for a Chinese pedigree affected with inherited afibrinogenemia.
For the proband and his family members, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrin(ogen) degradation products (FDPs), D-dimer (D-D), plasminogen activity (PLG:A) and the TT mixed experiment with protamine sulfate were determined with a STAGO-R automatic coagulation analyzer. The activity and antigen of fibrinogen (Fg) in plasma were measured with the Clauss method and immunonephelometry method, respectively. All exons and flanking regions of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR and directly sequenced. Human Splicing Finder software was used to predict and score the change of splicing site caused by the mutation.
The proband showed normal FDPs and D-D but significantly prolonged TT, PT and APTT. The activity and antigen of fibrinogen in plasma were significantly decreased (<0.1 g/L). His young sister and parents showed slightly prolonged TT (18.20-18.50 s) and decreased fibrinogen activity (1.27-1.54 g/L) and fibrinogen antigenic content (1.34-1.56 g/L). Genetic testing revealed that the proband has carried homozygous IVS7-12A>G (g.4147A>G) mutations of the FGG gene, for which his parents and young sister were heterozygous. As predicted by Human Splicing Finder and Mutation Taster software, the variant may generate a new splicing site which can extend the sequence of exon 7 by 11 bp, with alteration of the coding sequence. PROVEAN suggested the variant to be deleterious.
The afibrinogenemia of the proband may be attributed to the FGG IVS7-12A>G variant, which was unreported previously.
探究一个患遗传性无纤维蛋白原血症的中国家系的遗传基础。
对先证者及其家庭成员，采用STAGO-R自动凝血分析仪测定凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白（原）降解产物（FDPs）、D-二聚体（D-D）、纤溶酶原活性（PLG:A）以及硫酸鱼精蛋白TT混合试验。分别采用Clauss法和免疫比浊法测定血浆中纤维蛋白原（Fg）的活性和抗原。通过聚合酶链反应（PCR）扩增纤维蛋白原基因（FGA、FGB和FGG）的所有外显子及其侧翼区域，并进行直接测序。使用人类剪接预测软件预测并评估突变导致的剪接位点变化。
先证者FDPs和D-D正常，但TT、PT和APTT显著延长。血浆中纤维蛋白原的活性和抗原显著降低（<0.1 g/L）。他的妹妹和父母TT略有延长（18.20 - 18.50秒），纤维蛋白原活性（1.27 - 1.54 g/L）和纤维蛋白原抗原含量（1.34 - 1.56 g/L）降低。基因检测显示，先证者携带FGG基因纯合IVS-7-12A>G（g.4147A>G）突变，其父母和妹妹为杂合子。正如人类剪接预测软件和突变预测软件所预测的，该变异可能产生一个新的剪接位点，可使外显子7的序列延长11 bp，导致编码序列改变。蛋白变异效应分析工具（PROVEAN）提示该变异有害。
先证者的无纤维蛋白原血症可能归因于FGG基因IVS-7-12A>G变异，此前未见报道。
