纤维蛋白原是一种六聚体糖蛋白,由两组三种多肽组成(Aα,Bβ,和γ链,由三个基因FGA编码,FGB,和FGG)。它参与了凝固过程的最后阶段,为形成止血栓所必需的纤维蛋白单体的前体。罕见的遗传性纤维蛋白原紊乱可以表现为定量缺陷,定性缺陷,或者两者兼而有之。特别是,纤维蛋白原血症和低纤维蛋白原血症的特征是与正常或降低的抗原水平相关的功能活性降低,并且通常由影响三个纤维蛋白原基因中任何一个的杂合突变决定。在这项研究中,我们调查了7例无关患者的纤溶代谢异常和低纤溶代谢异常的遗传基础.突变筛查揭示了六种不同的变异,其中两个小说(FGB-p。Asp185Asn和FGG-p。Asn230Lys)。FGG-p的分子表征。Asn230Lys突变,通过重组突变蛋白的瞬时表达实验,证明它诱导纤维蛋白原分泌几乎完全受损,根据通常与定量纤维蛋白原疾病相关的分子机制。相反,FGB-P.Asp185Asn变体被证明是一种糖基化突变,导致Bβ链的高糖基化,不影响纤维蛋白原的组装和分泌。据我们所知,这是涉及FGB基因的第二个糖基化获得突变.
Fibrinogen is a hexameric glycoprotein consisting of two sets of three polypeptides (the Aα, Bβ, and γ chains, encoded by the three genes FGA, FGB, and FGG). It is involved in the final phase of the coagulation process, being the precursor of the fibrin monomers necessary for the formation of the hemostatic plug. Rare inherited fibrinogen disorders can manifest as quantitative deficiencies, qualitative defects, or both. In particular, dysfibrinogenemia and hypo-dysfibrinogenemia are characterized by reduced functional activity associated with normal or reduced antigen levels, and are usually determined by heterozygous mutations affecting any of the three fibrinogen genes. In this study, we investigated the genetic basis of dys- and hypo-dysfibrinogenemia in seven unrelated patients. Mutational screening disclosed six different variants, two of which novel (FGB-p.Asp185Asn and FGG-p.Asn230Lys). The molecular characterization of the FGG-p.Asn230Lys mutation, performed by transient expression experiments of the recombinant mutant protein, demonstrated that it induces an almost complete impairment in fibrinogen secretion, according to a molecular mechanism often associated with quantitative fibrinogen disorders. Conversely, the FGB-p.Asp185Asn variant was demonstrated to be a gain-of-glycosylation mutation leading to a hyperglycosylation of the Bβ chain, not affecting fibrinogen assembly and secretion. To our knowledge, this is the second gain-of-glycosylation mutation involving the FGB gene.