Background: Whereas the G20210A (c.*97G>A) prothrombin gene variant has been associated with an increased risk of venous thromboembolism (VTE), other rare mutations in F2 gene have been reported, with unknown frequency and potential association with VTE.
Aims: To report a case with a rare F2 mutation.
Methods: A 69 years old Caucasian woman presented with an unprovoked deep venous thrombosis of the leg. The thrombophilia work-up included standard coagulation tests, antithrombin, protein C, protein S, anticardiolipin and antibeta2GP1 antibodies, (isotypes G and M), lupus anticoagulant (LA) and F2 and F5 gene polymorphisms determination by melting curve analysis after real-time PCR on a capillary-based LightcyclerTM. Finally, sequencing of the 3’UTR region encompassing the 20210 position of the F2 gene was studied using an ABI 3500XL.
Results: Antithrombin, proteins C/S, anticardiolipin and antibeta2GP1B were within their normal ranges. LA was negative and F5 genotyping for G1691A transition revealed a wild-type genotype. By contrast, melting curve analysis for G20210A polymorphism showed an unusual curve progression (figure 1), with Tm (57.5°C and 63.5°C), whereas the melting points™ corresponding to the wild-type and the 20210 A allele were defined by the manufacturer to be between 61-67°C and 51-56°C, respectively. Sequencing revealed a C>T heterozygous transition at position 20209. The retrospective evaluation of test results obtained in our two hospitals between 2007 and 2018, revealed 21 heterozygous carriers of the C20209T mutation among 26.000 determinations (incidence: 0.08%).
Figure
Conclusions: The C20209T mutation detected in our patient is rare among Caucasians, and is mainly found in non-Caucasian patients particularly Africans, African-Americans and Caribbeans. Its role as VTE risk factor is still unknown and the frequency misjudged. One possible reason could rely on the widely used specific assays for the G20210A mutation such as the classical RFLP, in contrast with the LightcyclerTM used in the present study.
To cite this abstract in AMA style:
Jambou D, Saut N, Queyrel-Moranne V, Appert-Flory A, Fischer F, Suchon P, Toulon P. C20209T Prothrombin Gene Mutation in a Caucasian Woman with a History of Venous Thrombosis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/c20209t-prothrombin-gene-mutation-in-a-caucasian-woman-with-a-history-of-venous-thrombosis/. Accessed November 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/c20209t-prothrombin-gene-mutation-in-a-caucasian-woman-with-a-history-of-venous-thrombosis/