Neerman-Arbez Marguerite, de Moerloose Philippe, Casini Alessandro
Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Division of Angiology and Haemostasis, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Semin Thromb Hemost. 2016 Jun;42(4):356-65. doi: 10.1055/s-0036-1571340. Epub 2016 Mar 28.
Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified.
I型（纤维蛋白原定量缺陷），即低纤维蛋白原血症或无纤维蛋白原血症，分别表现为血浆纤维蛋白原抗原水平降低或缺失；II型（纤维蛋白原定性缺陷），即异常纤维蛋白原血症或低异常纤维蛋白原血症，其抗原水平正常或降低，同时伴有不成比例的低功能活性。这些疾病是由纤维蛋白原编码基因FGA、FGB和FGG的突变引起的。无纤维蛋白原血症与轻度至重度出血有关，而低纤维蛋白原血症通常无症状。对于这些定量性疾病，大多数突变会阻止蛋白质的产生。然而，在某些情况下，错义突变或晚期截短的无义突变允许突变纤维蛋白原链的合成，但细胞内纤维蛋白原的组装和/或分泌受损。定性纤维蛋白原疾病与出血、血栓形成或血栓形成和出血均有关，但许多异常纤维蛋白原血症是无症状的。大多数病例是由杂合错义突变引起的。在此，我们回顾纤维蛋白原基因异常的实验室和基因诊断，并对已确定的致病突变进行更新讨论。
