Abstract Number: PB0409
Meeting: ISTH 2021 Congress
Background: Congenital fibrinogen disorders (CFDs) are caused by mutations in FGA, FGB, FGG genes and are classified as quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia, hypodysfibrinogenemia) fibrinogen defects.
Aims: To identify the mutations that cause CFDs and to examine the genotype effect on clinical phenotype in patients with CFDs.
Methods: Thirteen Iranian patients with CFDs (Dysfibrinogenemia, n=10; hypodysfibrinogenemia, n=2 and Afibrinogenemia, n=1) within 9 unrelated families were included. Gene sequencing was performed following a polymerase chain reaction (PCR) amplification of FGA, FGB, FGG genes. Routine and specific laboratory tests such as fibrinogen antigen (Fib:Ag) and Clauss fibrinogen assay (Fib:C) were performed and ISTH Bleeding Assessment Tool (ISTH-BAT) was also evaluated.
Results: Patients’ characteristics were summarized in table 1. We identified 6 different but previously reported mutations located on FGA exon 2 (61%), exon 4 (8%), exon 5 (8%), and FGG exon 8 (23%). Variants are including p.Arg38Thr, p.Arg35His/Cys in FGA exon 2, p.Val145Asp in FGA exon 4, p.Gly316GlufsX105 in FGA exon 5, and p.Arg301Cys in FGG exon 8. In patient 5 we also identified two polymorphisms in FGA: c.510+37C>T (intron 4) and p.Thr312Ala (exon 5). Functional consequences of the former variant are unclear, while the last one is reported to be associated with the risk of venous thrombosis, but our patient has not experienced thrombosis. In patients with dysfibrinogenemia, two hotspot mutations (Arg35 and Arg301) were identified in 60%: p.Arg35His (20%), p.Arg35cys (10%), and p.Arg301Cys (30%), and the remaining patients (40%) had p.Arg38Thr mutation. The p.Arg301Cys was observed in both dysfibrinogenemia and hypodysfibrinogenemia in the same affected family members. The overall median bleeding score (BS) was 4 (range 0-5) and it was 3.5 (range 0-5) in dysfibrinogenemia. Cutaneous bleeding (64%) and menorrhagia (43%) were the common bleeding manifestations.
|Family||Patient||Age at diagnosis/sex||Fib:C /Fib:Ag (mg/dl)||Phenotype||Gene/
| 63y /F
| 8y /M
| 15y /F
18 y /F
|VIII||12||3y /F||65/156||Mild hypodysfibrinogenemia||FGA/4||p.Val145Asp||Hetero||4|
Conclusions: We found several mutations with variable BS indicating that there was a weak genotype-phenotype correlation in CFDs.
To cite this abstract in AMA style:Mohsenian S, Azarkeivan A, Mirakhorli M, Jazebi M, OS. Clinical and Molecular Characterization of Iranian Patients with Congenital Qualitative Fibrinogen Disorders [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/clinical-and-molecular-characterization-of-iranian-patients-with-congenital-qualitative-fibrinogen-disorders/. Accessed December 8, 2021.
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