Mouse Anti-Human FGG monoclonal antibody, clone 567

Hepatic fibrinogen storage disease is a rare autosomal dominant genetic disorder characterized by hypofibrinogenemia, as well as the retention of variant fibrinogen within the hepatocellular endoplasmic reticulum. Here, we describe an asymptomatic 4-year-old boy with abnormal liver function test results and unexpected hypofibrinogenemia. Liver biopsy showed circular eosinophil inclusion bodies in the hepato-cytoplasm. Immunostaining results of eosinophil inclusion bodies were positive for fibrinogen. Following pretreatment with diastase, the inclusion bodies failed to stain with the periodic acid-Schiff technique; moreover, immunostaining results were positive for fibrinogen, but negative for alpha-1-antitrypsin. Genetic analysis identified a heterozygous missense mutation c.1201C > T (p. Arg401Trp) within the fibrinogen gamma-chain (FGG) gene and an additional single nucleotide polymorphism c.-58 A > G within the 5'-untranslated region of the fibrinogen A alpha-chain (FGA) gene. Thus, the patient was diagnosed with hepatic fibrinogen storage disease. Our results indicate that, for patients who exhibit chronic liver disease with unexpected hypofibrinogenemia, hepatic fibrinogen storage disease should be considered in the differential diagnosis. Moreover, our findings emphasize the importance of molecular diagnosis in patients with cryptogenic liver disease.

Introduction: Thrombin-induced conversion of fibrinogen to fibrin plays an essential rote in hemostasis and results in the stabilization of thrombi. Elevated plasma fibrinogen levels have been associated with both increased plasma viscosity and platelet aggregabitity. Recently, a haplotype-tagging single nucleotide polymorphism characterized by a C to T substitution at nucleotide 10034 of the fibrinogen gamma gene (FGG 10034C > T, rs2066865), has been proposed as a novel risk factor for deep venous thrombosis (DVT). Aim of the present study was to provide further data on the rote of the FGG 10034C > T polymorphism for DVT. Materials and methods: FGG genotypes were determined by 5'-exonuclease assay (TaqMan) in 358 patients with documented DVT and a total of 783 control subjects. Results: In a multivariate analysis adjusting forage, sex, presence of factor V Leiden and carriage of prothrombin 20210A, homozygosity for the FGG 10034 TT genotype yielded an odds ratio of 2.01 (95% Cl 1.23-3.31; p=0.006) for DVT. Conclusions: Our data confirm the primary finding that the FGG 10034C > T polymorphism is associated with DVT risk. (c) 2007 Elsevier Ltd. All rights reserved.