Identification and molecular pathogenesis study of a case of inherited dysfibrinogenemia / 临床检验杂志

ABSTRACT

Objective@#To analyze the phenotype and genotype of a Chinese pedigree with inherited dysfibrinogenaemia and investigate the molecular mechanism of the disease. @*Methods@#Venous blood samples were collected from all family members, and routine coagulation tests were conducted. Functional fibrinogen in venous blood samples was measured by Clauss method, and the antigen level of fibrinogen in plasma was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of the three fibrinogen genes were analyzed by direct sequencing. Fibrinogen electrophoresis, fibrinogen clottability measurement, fibrin polymerisation measurement and electron microscopy scanning were also used to investigate the molecular characteristics and pathogenesis. @*Results@#The proband had normal activated partial thromboplastin time, prothrombin time and plasma fibrinogen antigen, but prolonged thrombin time, prolonged reptilase time and reduced fibrinogen activity level, which were also found in his father. The sequencing results of the proband revealed heterozygous A1211G in the exon 2 of FGA gene originating from his father, which caused Arg19Gly missense mutation. The western-blot results showed that no abnormal bands of plasma fibrinogen were found in the proband and his father. Both thrombin-induced fibrin polymerisation and reptilase induced fibrin polymerisation were significantly impaired compared to normal control. Fibrinogen clottability measurement showed that only about 20.8% molecules of plasma fibrinogen in the proband were involved in the clot formation. Scanning electron microscopy revealed that the proband′s average fibre diameters were found to be significantly thicker than that of the control(P＜0.001), and the density was smaller than that of normal control. @*Conclusion@#The Arg19Gly mutation should be responsible for the proband′s dysfibrinogenaemia and the relevant clinical symptoms.