Identification and characterization of novel mutations implicated in congenital fibrinogen disorders

GUGLIELMONE, HUGO

Research and Practice in Thrombosis and Haemostasis

Wiley Online

Lugar: New Yersey; Año: 2018 vol. 2 p. 800 - 800

ntroduction: Fibrinogen is a complex molecule comprised of two sets of Aα, Bβ, and γchains. Fibrinogen deficiencies can lead to the development of bleeding or thromboembolicevents. The objective of this study was to perform DNA sequence analysis of patientswith clinical fibrinogen abnormalities, and to perform genotype-phenotypecorrelations.Materials and Methods: DNA from 31 patients was sequenced to evaluate disease-causingmutations in the three fibrinogen genes: FGA, FGB, and FGG. Clinical datawere extracted from medical records or from consultation with referring hematologists.Fibrinogen antigen and functional (Clauss method) assays, as well as reptilasetime (RT) and thrombin time (TT) were obtained for each patient. Molecular modelingwas used to simulate the functional impact of specific missense variants on the overallprotein structure.Results: Seventeen mutations, including six novel mutations, were identified in thethree fibrinogen genes. There was little correla