Research Article: Homozygous missense variant F12 (Gly506Asp) associated with severe factor XII deficiency: a case report
Abstract:
Factor XII deficiency can be related to either homozygous or compound heterozygous pathogenic variants in the F12 gene. The disease is commonly known as Hageman trait and is inherited in both autosomal recessive or dominant patterns. Clinically, factor XII deficiency is not associated with bleeding but conversely has been linked to thrombotic events, recurrent pregnancy loss, and hereditary angioedema. Molecular data of F12 deficiency are scarce and have revealed varying results between cases. However, most of the reported variants are missense mutations, gross deletions, or small insertion. Factor XII deficiency has been reported in the Saudi population in several studies, either as isolated case reports or included within the studies of rare bleeding factors deficiency. However, molecular data are lacking as no case report of genetic studies related to factor XII deficiency has been published in our local population, to the best of our knowledge.
Introduction:
Factor XIIa plays a key role in converting prekallikrein to kallikrein, which in turn cleaves factor XII (FXII) to heavy chain alpha-factor XIIa and light chain beta-factor XIIa. Alpha-factor XII helps in initiation of fibrinolysis system by converting plasminogen into plasmin, resulting in fibrin degradation. Furthermore, FXII has an integral role in generation of bradykinin, a protein that promotes inflammation by increasing vessel wall permeability [1,2,3].
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