A distinct common p.Gln317* mutation among causative LMAN1 genetic mutations of combined factor V and factor VIII deficiency in five Taiwanese families
Abstract
Dear Editor, In the coagulation system, coagulation factor V (FV) and factor VIII (FVIII) are structurally and functionally homologous proteins. Once activated through proteolysis, both activated FV (FVa) and activated FVIII (FVIIIa) act as essential cofactors to the serine protease factor Xa (FXa) and factor IXa, respectively. In the presence of Ca2+ ions, these protein complexes assemble on a negatively charged membrane surface, resulting in the formation of prothrombinase and intrinsic tenase complexes, respectively. Both of the latter contribute to the subsequent generation of thrombin. Combined deficiency of FV and FVIII (F5F8D, OMIM 227300) is an autosomal recessive bleeding disease, which is characterized by a concordant decrease in plasma FV and FVlll levels to 5–30% of the normal levels, with a mild-to-moderate bleeding tendency. After the discovery of a bleeding tendency related to deficiency of both FV and FVIII as a distinct disease entity in two siblings by Oeri et al. in 1954,1 the inherited bleeding diathesis was quickly recognized not to have been caused by the coincidence of parahaemophilia (FVdeficiency) andhaemophilia A (FVIII deficiency). Since then, the pathogenesis of F5F8D remained unclear for years until the identification of two responsible genes, namely LMAN1 (lectin, mannose-binding 1) andMCFD2 (multiple coagulation factor deficiency protein 2). According to the Report of 2019Annual Global Survey published by theWorld Federation of Haemophilia, a…
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