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

Abstract

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 (interquartile 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.