A case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene. Issue 4 (3rd May 2021)

• Record Type: Journal Article
• Authors: Mansory, Eman M.; Bhai, Pratibha; Stuart, Alan; Laudenbach, Lori; Sadikovic, Bekim; Lazo‐Langner, Alejandro
• Is Part Of: Research and practice in thrombosis and haemostasis. Volume 5:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-03
• Subjects: bleeding disorder -- dysprothrombinemia -- hypoprothrombinemia -- prothrombin deficiency -- prothrombin mutation; Thrombosis -- Periodicals; Hemostasis -- Periodicals; 616.135005
• DOI: 10.1002/rth2.12510
• Languages: English
• ISSNs: 2475-0379

Abstract

Abstract: Congenital prothrombin deficiency is an extremely rare, autosomal recessive bleeding disorder with a prevalence of 1 in 2 million individuals. Here, we report a case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene (F2), affecting the heavy B chain. The patient presented with a history of multiple bleeding events in his youth that are mostly trauma associated, with a family history of prothrombin deficiency. Laboratory analysis showed a prolonged activated partial thromboplastin time and a prothrombin activity level of 5%. Genetic analysis of the F2 gene identified two heterozygous variants; one is a previously reported pathogenic deletion (c.1814_1815del; p.His605Argfs*13), and the other is a novel missense variant (c.1147C>T; p.Arg383Trp). In silico analysis predicted that p.Arg383Trp is likely to be disease causing, as it affects one of the anion‐binding exosites‐I of the B chain. This case highlights the significance of molecular findings in confirming the diagnosis of patients with congenital prothrombin deficiency.