Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders
Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders
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DOI：
10.1055/s-0036-1571340
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发表时间：
2016-06-01
影响因子：
5.7
通讯作者：
Casini, Alessandro
中科院分区：
文献类型：
--
作者：
Neerman-Arbez, Marguerite;de Moerloose, Philippe;Casini, Alessandro
先天性纤维蛋白原疾病分为两种类型的血浆纤维蛋白原缺陷：I型（定量纤维蛋白原缺乏），即低纤维蛋白原血症或无纤维蛋白原血症，其中分别存在低或缺乏血浆纤维蛋白原抗原水平，和II型（定性纤维蛋白原缺乏），即异常纤维蛋白原血症或低异常纤维蛋白原血症，其中存在与不成比例的低功能活性相关的正常或降低的抗原水平。这些疾病是由三种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。对于这些数量障碍，大多数突变阻止蛋白质产生。然而，在某些情况下，错义或晚期截短无义突变允许合成突变的纤维蛋白原链，但细胞内纤维蛋白原组装和/或分泌受损。定性纤维蛋白原异常与出血、血栓形成或血栓形成和出血有关，但许多异常纤维蛋白原血症无症状。大多数病例是由杂合错义突变引起的。在这里，我们回顾了纤维蛋白原基因异常的实验室和遗传学诊断，并对确定的致病突变进行了最新的讨论。
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.