Mutations in inherited fibrinogen disorders correlated with clinical features in the Chinese population

Abstract

Two probands with unknown reasons for low fibrinogen activity were considered to investigate the association between mutations in inherited fibrinogen disorders (IFDs) and clinical features in the Chinese population. A routine coagulation test was conducted on a Sysmex CS5100 coagulation analyzer, and Sanger sequencing was employed to analyze mutations. A PubMed database search through May 2020 was performed to identify relevant studies regarding the congenital fibrinogen disorder epidemic in China. A common heterozygous missense mutation (c.1233G > A p.Arg35His), a novel heterozygous mutation (c.2014T > C p.Trp672Arg), and a novel homozygous mutation (c.16A > G p.Ile6Val) in the FGA gene were identified in two probands with dysfibrinogenemia. The global coagulation screening assay can distinguish four types of IFD, especially a ratio of Fib:Ag/Fib:C equal to 1.5, which can distinguish patients with hypofibrinogenemia from those with hypodysfibrinogenemia. A total of 81 mutations from 76 probands in 45 IFD families have been reported in the Chinese population. Arg35 in FGA and Arg301 in FGG were responsible for IFD in more than half of patients in the Chinese population. It is possible to distinguish four types of IFD by using a global coagulation screening assay. Mutations in FGA, FGB and FGG occur in different functional regions, and Arg changes account for more than 70% of patients with IFD in the Chinese population, especially Arg-Cys, which may be associated with severe clinical symptoms.