Objective: To detect and analyze coagulation related indexes and genotypes of a patient with congenital fibrinogen deficiency and his family members, and to investigate the possible molecular pathogenesis.
Methods: Four peripheral blood samples (proband and 3 family members) were collected and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), D-Dimer and eight coagulation factor indicators were detected. All exons and flanking sequences of the FGA, FGB, and FGG genes encoding the three peptide chains of fibrinogen were sequenced and analyzed by bioinformatics.
Results: Among the eight coagulation factors of the proband and the elder sister, F Ⅴ and F Ⅷ were slightly higher, TT was significantly prolonged, and Fg was significantly reduced. Sequencing results showed that c.901C>T heterozygous mutation existed in the FGG gene. Bioinformatics analysis showed that the mutation changed the original protein structure and reduced the number of hydrogen bonds.
Conclusion: The fibrinogen gamma chain c.901C>T heterozygous mutation is the main cause of congenital fibrinogen deficiency in this family. This mutation is reported for the first time at home and abroad.
题目: 新型FGG基因突变导致遗传性纤维蛋白原缺陷症的研究.
目的: 对临床发现的1例遗传性纤维蛋白原缺陷症患者及其家属进行凝血相关指标检测和基因型分析，并探讨可能的分子发病机制.
方法: 采集先证者及其家属共4人的外周血，检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（Fg）、D-二聚体及8项凝血因子指标。对编码纤维蛋白原3条肽链的FGA、FGB和FGG基因的所有外显子和侧翼序列进行测序并进行生物信息学分析.
结果: 先证者及其长姐的8项凝血因子中FⅤ、FⅧ稍高，TT明显延长，Fg明显降低；测序结果显示FGG基因存在c.901C>T杂合突变。生物信息学分析显示，突变改变了原有的蛋白结构，减少了氢键数目.
结论: 纤维蛋白原γ链c.901C>T杂合突变是引起该家系遗传性纤维蛋白原缺陷的主要原因，该突变是首次在国内外报道.