Clinical and Genetic Characterization of 51 Patients with Congenital Fibrinogen Disorders from China

Objective To investigate the classification, clinical manifestations, laboratory findings, and genetic mutations associated with hereditary fibrinogen disorders in Chinese population. Methods Between February 2015 and February 2022, 65 patients with congenital fibrinogen disorders (CFD) were identified at Wuhan Union Hospital. Comprehensive data were available for 51 patients, allowing for a retrospective analysis. Results The cohort comprised 17 males (33.3%) and 34 females (66.7%), with a median diagnosis age of 35.0 years (interquar tile range: 25.5-42.5). Of the patients, 35 (68.6%) were diagnosed with dysfibrinogenemia, 8 (15.7%) with hypofibrinogenemia, 7 (13.7%) with hypodysfibrinogenemia, and 1 (2.0%) with afibrinogenemia. The median diagnosis ages for the asymptomatic, Grade 1, Grade 2, and Grade 3 groups were 44.5 years (range: 37-58.5), 28 years (22.5-36.5), 35.5 years (21.75-41), and 28 years (22.75-30.75), respectively. The asymptomatic group had the latest diagnosis age, whereas Grade 3 had the earliest. A negative correlation was observed between Fg:C levels and bleeding severity (rs=- 0.2937, p = 0.0365). In total, 52 variants were found in 51 unrelated patients, with one patient carrying two mutations. The 37 distinct mutations included 11 in FGA, 3 in FGB, and 23 in FGG. Conclusion This study investigates the clinical, laboratory, and genetic characteristics of patients with CFD in China, revealing a negative correlation between Fg:C levels and bleeding severity. Female patients are at higher risk for gynecological complications due to physiological traits. Additionally, R35 in FGA and R301 in FGG were identified as hotspot mutations.