Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland.
Int J Mol Sci. 2018 Jan 8;19(1):192. doi: 10.3390/ijms19010192.
The study of inherited fibrinogen disorders, characterized by extensive allelic heterogeneity, allows the association of defined mutations with specific defects providing significant insight into the location of functionally important sites in fibrinogen and fibrin. Since the identification of the first causative mutation for congenital afibrinogenemia, studies have elucidated the underlying molecular pathophysiology of numerous causative mutations leading to fibrinogen deficiency, developed cell-based and animal models to study human fibrinogen disorders, and further explored the clinical consequences of absent, low, or dysfunctional fibrinogen. Since qualitative disorders are addressed by another review in this special issue, this review will focus on quantitative disorders and will discuss their diagnosis, clinical features, molecular bases, and introduce new models to study the phenotypic consequences of fibrinogen deficiency.
遗传性纤维蛋白原紊乱的研究具有广泛的等位基因异质性，可将特定突变与特定缺陷相关联，从而深入了解纤维蛋白原和纤维蛋白中功能重要部位的位置。自首次发现先天性无纤维蛋白血症的致病突变以来，研究已经阐明了导致纤维蛋白原缺乏的众多致病突变的潜在分子病理生理学，开发了基于细胞和动物的模型来研究人类纤维蛋白原紊乱，并进一步探讨了无纤维蛋白原、低纤维蛋白原或功能失调纤维蛋白原的临床后果。由于定性紊乱在本期特刊中的另一篇综述中已有介绍，因此本篇综述将重点介绍定量紊乱，并将讨论其诊断、临床特征、分子基础，并介绍新的模型来研究纤维蛋白原缺乏的表型后果。
